WO2012067965A1 - Nampt and rock inhibitors - Google Patents

Nampt and rock inhibitors Download PDF

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Publication number
WO2012067965A1
WO2012067965A1 PCT/US2011/060425 US2011060425W WO2012067965A1 WO 2012067965 A1 WO2012067965 A1 WO 2012067965A1 US 2011060425 W US2011060425 W US 2011060425W WO 2012067965 A1 WO2012067965 A1 WO 2012067965A1
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WO
WIPO (PCT)
Prior art keywords
dihydro
carboxamide
isoindole
phenyl
carbamoyl
Prior art date
Application number
PCT/US2011/060425
Other languages
French (fr)
Inventor
Michael L. Curtin
Bryan K. Sorensen
Howard R. Heyman
Richard F. Clark
Kevin R. Woller
Omar J. Shah
Michael Michaelides
Chris Tse
Anil Vasudevan
Helmut Mack
Todd M. Hansen
Ramzi Sweis
Marina A. Pliushchev
Original Assignee
Abbott Laboratories
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=45034200&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2012067965(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to CN2011800647158A priority Critical patent/CN103313968A/en
Priority to CA2816594A priority patent/CA2816594A1/en
Priority to JP2013538943A priority patent/JP6117104B2/en
Priority to AU2011329233A priority patent/AU2011329233A1/en
Priority to KR1020137015348A priority patent/KR20140009251A/en
Application filed by Abbott Laboratories filed Critical Abbott Laboratories
Priority to SG2013037643A priority patent/SG190819A1/en
Priority to BR112013012078A priority patent/BR112013012078A2/en
Priority to EP11787996.5A priority patent/EP2640698A1/en
Priority to RU2013126657/04A priority patent/RU2013126657A/en
Priority to MX2013005454A priority patent/MX2013005454A/en
Publication of WO2012067965A1 publication Critical patent/WO2012067965A1/en
Priority to IL225862A priority patent/IL225862A0/en
Priority to AU2017200079A priority patent/AU2017200079A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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Definitions

  • This invention pertains to compounds which inhibit the activity of NAMPT, compositions containing the compounds, and methods of treating diseases during which NAMPT is expressed. This invention also pertains to compounds which inhibit the activity of ROCK, compositions containing the compounds, and methods of treating diseases during which ROCK is expressed.
  • NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays a critical role in many physiologically essential processes (Ziegkel, M. Eur. J. Biochem. 267,1550-1564, 2000). NAD is necessary for several signaling pathways including among others poly ADP- ribosylation in DNA repair, mono-ADP-ribosylation in both the immune system and G- protein-coupled signaling, and NAD is also required by sirtuins for their deacetylase activity (Garten, A. et al Trends in Endocrinology and Metabolism, 20, 130-138, 2008).
  • NAMPT also known as pre-B-cell-colony-enhancing factor (PBEF) and visfatin
  • PBEF pre-B-cell-colony-enhancing factor
  • visfatin is an enzyme that catalyzes the phosphoribosylation of nicotinamide and is the rate-limiting enzyme in one of two pathways that salvage NAD.
  • NAMPT inhibitors have potential as anticancer agents. Cancer cells have a higher basal turnover of NAD and also display higher energy requirements compared with normal cells. Additionally, increased NAMPT expression has been reported in colorectal cancer (Van Beijnum, J.R. et al Int. J. Cancer 101, 118-127, 2002) and NAMPT is involved in angiogenesis (Kim, S.R. et al. Biochem. Biophys. Res. Commun. 357, 150-156, 2007). Small-molecule inhibitors of NAMPT have been shown to cause depletion of intracellular NAD+ levels and ultimately induce tumor cell death (Hansen, CM et al. Anticancer Res. 20, 42111-4220, 2000) as well as inhibit tumor growth in xenograft models (Olese, U.H. et al. Mol Cancer Ther. 9, 1609-1617, 2010).
  • NAMPT inhibitors also have potential as therapeutic agents in inflammatory and metabolic disorders (Galli, M. et al Cancer Res. 70, 8-11, 2010).
  • NAMPT is the predominant enzyme in T and B lymphocytes.
  • Selective inhibition of NAMPT leads to NAD+ depletion in lymphocytes blocking the expansion that accompanies autoimmune disease progression whereas cell types expressing the other NAD+ generating pathways might be spared.
  • a small molecule NAMPT inhibitor (FK866) has been shown to selectively block proliferation and induce apoptosis of activated T cells and was efficacious in animal models of arthritis (collagen -induced arthritis) (Busso, N.et al. Plos One 3, e2267, 2008).
  • FK866 ameliorated the manifestations of experimental autoimmune encephalomyelitis (EAE), a model of T-cell mediated autoimmune disorders.
  • EAE experimental autoimmune encephalomyelitis
  • NaMPT activity increases NF-kB transcriptional activity in human vascular endothelial cell, resulting in MMP-2 and MMP-9 activation, suggesting a role for NAMPT inhibitors in the prevention of inflammatory mediated complications of obesity and type 2 diabetes (Adya, R. et. Al. Diabetes Care, 31, 758-760, 2008).
  • Rho kinases the first Rho effectors to be described, are serine/threonine kinases that are important in fundamental processes of cell migration, cell proliferation and cell survival. Abnormal activation of the Rho ROCK pathway has been observed in various disorders. Examples of disease states in which compounds with ROCK inhibition have potentially beneficial therapeutic effects due to their anti vasospasm activity includes cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension and atherosclerosis. This muscle relaxing property is also beneficial for treating asthma, male erectile dysfunctions, female sexual dysfunction, and over-active bladder syndrome.
  • cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension and atherosclerosis. This muscle relaxing property is also beneficial for treating asthma, male erectile dysfunctions, female sexual dysfunction, and over
  • Rho ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury).
  • Rho ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury).
  • Rho/ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury).
  • Rho ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury,
  • compounds of the invention can be used as treatment for neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and inflammatory pain, as well as other diseases such as rheumatoid arthritis, osteoarthritis, asthma, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, Lupus, and inflammatory bowel disease.
  • neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and inflammatory pain
  • other diseases such as rheumatoid arthritis, osteoarthritis, asthma, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, Lupus, and inflammatory bowel disease.
  • ROCK inhibitors reduce cell proliferation and cell migration, they could be useful in treating cancer and tumor metastasis. Further more, there is evidence suggesting that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in anti-viral and anti-bacterial applications. ROCK inhibitors are also useful for the treatment of insulin resistance and diabetes. Further, ROCK inhibitors have been shown to ameliorate progression of cystic fibrosis (Abstract S02.3, 8th World Congress on Inflammation, Copenhagen, Denmark, June 16-20, 2007).
  • Rho-associated coiled-coil forming protein kinases (ROCK)-l and -2, have been shown to enhance myosin light chain (MLC) phosphorylation by inhibiting MLC phosphatase as well as phosphorylating MLC. This results in the regulation of actin-myosin contraction.
  • ROCK myosin light chain
  • Rho ROCK pathway may be useful for the treatment of asthma.
  • One embodiment of this invention pertains to compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT or ROCK, the compounds having Formula (Ic)
  • X 1 , X 2 , and X 3 are CH; or
  • X 1 and X 3 are CH; and X 2 is N; or X 1 and X 3 are CH; and X 2 is CR 1 ; or
  • X 2 and X 3 are CH; and X 1 is CR 1 ; or
  • X 1 is CH; and X 2 and X 3 are CR 1 ; or
  • X 2 is CH; and X 1 and X 3 are N; or
  • X 2 and X 3 are CH; and X 1 is N; or
  • X 1 is CH; X 2 is N; and X 3 is CR 1 ; or
  • X 1 is N;
  • X 2 is CR 1 ; and
  • X 3 is N;
  • R 1 is R 3 , OR 3 , SR 3 , S(0)R 3 , S0 2 R 3 , C(0)R 3 , C(0)OR 3 , OC(0)R 3 , NHR 3 , N(R 3 ) 2 ,
  • R 2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • each R 2 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 4 , OR 4 , SR 4 , S(0)R 4 , S0 2 R 4 , C(0)R 4 , CO(0)R 4 , OC(0)R 4 , OC(0)OR 4 , NHC(0)R 4 , NR 4 C(0)R 4 , NHS(0) 2 R 4 , NR 4 S(0) 2 R 4 , NHC(0)OR 4 , NR 4 C(0)OR 4 , NHC(0)NH 2 , NHC(0)NHR 4 , NHC(0)N(R 4 ) 2 , NR 4 C(0)NHR 4 , NR 4 C(0)N(R 4 ) 2 , C(0)NH 2 , C(0)NHR 4 , C(0)N(R 4 ) 2 , C(0)NHOH, C(0)NHOR 4 , C(0)NHS0 2 R 4 , C(0)NR 4 S0 2 R 4 , C(0)NHOH, C(0)NHOR 4 ,
  • each R 2 phenyl is optionally substituted at the para position with one independently selected R 5 , OR 5 , SR 5 , S(0)R 5 , S0 2 R 5 , C(0)R 5 , CO(0)R 5 , OC(0)R 5 , OC(0)OR 5 , NH 2 , NHR 5 , N(R 5 ) 2 , NHC(0)R 5 , NR 5 C(0)R 5 , NHS(0) 2 R 5 , NR 5 S(0) 2 R 5 , NHC(0)OR 5 , NR 5 C(0)OR 5 , NHC(0)NH 2 , NHC(0)NHR 5 , NHC(0)N(R 5 ) 2 , NR 5 C
  • C(0)NHOR 6 C(0)NHS0 2 R 6 , C(0)NR 6 S0 2 R 6 , S0 2 NH 2 , S0 2 NHR 6 , S0 2 N(R 6 ) 2 , C(0)H, C(0)OH, OH, (O), CN, N 3 , N0 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, CI, Br or I;
  • R 4 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl; wherein each R 4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 7 , OR 7 , SR 7 , S(0)R 7 , S0 2 R 7 , C(0)R 7 , OC(0)R 7 , OC(0)OR 7 , NH 2 , NHR 7 , NHC(0)R 7 , NR 7 C(0)R 7 , NHS(0) 2 R 7 ,
  • R 5 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 9 , OR 9 , SR 9 , S(0)R 9 , S0 2 R 9 , C(0)R 9 , CO(0)R 9 , OC(0)R 9 , OC(0)OR 9 , NH 2 , NHR 9 , N(R 9 ) 2 , NHC(0)R 9 , NR 9 C(0)R 9 , NHS(0) 2 R 9 , NR 9 S(0) 2 R 9 , NHC(0)OR 9 , NR 9 C(0)OR 9 , NHC(0)NH 2 ,
  • R 6 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 10 , OR 10 , SR 10 , S(0)R 10 , S0 2 R 10 , NHR 10 , N(R 10 ) 2 , C(0)R 10 , C(0)NH 2 , C(0)NHR 10 , C(O)N(R 10 ) 2 , NHC(0)R , NR 1U C(0)R , NHS0 2 R , NHC(0)OR , S0 2 NH 2 , S0 2 NHR 1U , S0 2 N(R 1U ) 2 , NHC(0)NH 2 , NHC(0)NHR 10 , OH, (O), C(0)OH, N 3 , CN, NH 2 , CF
  • R 7 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 11 , OR 11 , SR. 11 , S(0)R n , S0 2 R n , NHR 11 , N(R n ) 2 , C(0)R n , C(0)NH 2 , C(0)NHR n , C(0)N(R n ) 2 ,
  • NHC(0)R n NR n C(0)R n , NHS0 2 R n , NHC(0)OR n , S0 2 NH 2 , S0 2 NHR n , S0 2 N(R n ) 2 , NHC(0)NH 2 , NHC(0)NHR n , OH, (O), C(0)OH, N 3 , CN, NH 2 , CF 3 , CF 2 CF 3 , F, CI, Br or I;
  • R 8 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 12 , OR 12 , SR 12 , S(0)R 12 , S0 2 R 12 , NHR 12 , N(R 12 ) 2 , C(0)R 12 , C(0)NH 2 , C(0)NHR 12 , C(0)N(R 12 ) 2 ,
  • R 9 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
  • R 10 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • R 11 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • R 12 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
  • R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are optionally substituted with one, two, three, four, five, or six independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S0 2 R 13 , C(0)R 13 , CO(0)R 13 , OC(0)R 13 , OC(0)OR 13 , NH 2 , NHR 13 , N(R 13 ) 2 , NHC(0)R 13 , NR 13 C(0)R 13 , NHS(0) 2 R 13 , NR 13 S(0) 2 R 13 , NHC(0)OR 13 , NR 13 C(0)OR 13 , NHC(0)NH 2 , NHC(0)NHR 13 , NHC(0)N(R 13 ) 2 , NR 13 C(0)NHR 13 , NR 13 C(0)N(R 13 ) 2 , C(0)NH 2 , C(0)NHR 13 , C(0)N(R 13 ) 2 , C(0)NH 2
  • R 13 is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkeny
  • R 14 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH 2 , S0 2 NH 2 , C(0)H, C(0)OH, OH, (O), CN, N 3 , N0 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, CI, Br or I; wherein each R 14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R 16 , OR 16 , OH, F, CI, Br, or I; wherein the R 16 alkyl is optionally substituted with one, two, three or four independently selected R 16
  • R 15 at each occurrence, is independently selected alkyl; wherein the R 15 alkyl is optionally substituted with one, two, three or four alkoxy;
  • R 16 at each occurrence, is independently selected alkyl, wherein the R 16 alkyl is optionally substituted with one, two, three or four alkoxy;
  • R 2 is unsubstituted alkyl or optionally substituted alkyl;
  • R 2 is C 4 -C 6 -alkyl;
  • X 1 , X 2 , and X 3 are CH; or
  • X 1 and X 3 are CH; and X 2 is N; or
  • X 1 and X 3 are CH; and X 2 is CR 1 ; or
  • X 2 and X 3 are CH; and X 1 is CR 1 ; or
  • X 1 is CH; and X 2 and X 3 are CR 1 ; or
  • X 2 is CH; and X 1 and X 3 are N; or
  • X 2 and X 3 are CH; and X 1 is N; or
  • X 1 is CH; X 2 is N; and X 3 is CR 1 ; or
  • X 1 is N;
  • X 2 is CR 1 ; and
  • X 3 is N;
  • R 1 is R 3 , OR 3 , SR 3 , S(0)R 3 , S0 2 R 3 , C(0)R 3 , C(0)OR 3 , OC(0)R 3 , NHR 3 , N(R 3 ) 2 , C(0)NH 2 , C(0)NHR 3 , C(0)N(R 3 ) 2 , NHC(0)R 3 , NR 3 C(0)R 3 , NHC(0)OR 3 , NR 3 C(0)OR 3 , S0 2 NH 2 , S0 2 NHR 3 , S0 2 N(R 3 ) 2 , NHS0 2 R 3 , NR 3 S0 2 R 3 , NHS0 2 NHR 3 , NHS0 2 N(R 3 ) 2 , NR 3 S0 2 NHR 3 , NR 3 S0 2 N(R 3 ) 2 , C(0)NHS0 2 R 3 , NHS0 2 NHR 3 , F, CI, Br, I, CN, NH 2 , N0 2 , N 3 ,
  • R 3 is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R 3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 6 , OR 6 , SR 6 , S(0)R 6 , S0 2 R 6 , C(0)R 6 , CO(0)R 6 , OC(0)R 6 , OC(0)OR 6 , NH 2 , NHR 6 , N(R 6 ) 2 , NHC(0)R 6 , NR 6 C(0)R 6 , NHS(0) 2 R 6 , NR 6 S(0) 2 R 6 , NHC(0)OR 6 , NR 6 C(0)OR 6 , NHC(0)NH 2 , NHC(0)NHR 6 , NHC(0)N(R 6 ) 2 , NR 6 C(0)N(R 6 ) 2 , NR 6 C(0)N(R 6 ) 2 , C(0)NH 2 , C(0)NHR 6 , C
  • R 5 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 9 , OR 9 , SR 9 , S(0)R 9 , S0 2 R 9 , C(0)R 9 , CO(0)R 9 , OC(0)R 9 , OC(0)OR 9 , NH 2 , NHR 9 , N(R 9 ) 2 , NHC(0)R 9 , NR 9 C(0)R 9 , NHS(0) 2 R 9 , NR 9 S(0) 2 R 9 , NHC(0)OR 9 , NR 9 C(0)OR 9 , NHC(0)NH 2 , NHC(0)NHR 9 , NHC(0)N(R 9 ) 2 , NR 9 C(0)NHR 9 , NR 9 C(0)N(R 9 ) 2
  • R 6 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 10 , OR 10 , SR 10 , S(0)R 10 , S0 2 R 10 , NHR 10 , N(R 10 ) 2 , C(0)R 10 , C(0)NH 2 , C(0)NHR 10 , C(O)N(R 10 ) 2 ,
  • NHC(0)R 10 NR 10 C(O)R 10 , NHS0 2 R 10 , NHC(0)OR 10 , S0 2 NH 2 , S0 2 NHR 10 , SO 2 N(R 10 ) 2 , NHC(0)NH 2 , NHC(0)NHR 10 , OH, (O), C(0)OH, N 3 , CN, NH 2 , CF 3 , CF 2 CF 3 , F, CI, Br or I;
  • R 9 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
  • R 10 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • R 3 , R 5 , R 6 , R 9 , and R 10 are optionally substituted with one, two, three, four, five, or six independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S0 2 R 13 , C(0)R 13 , CO(0)R 13 , OC(0)R 13 , OC(0)OR 13 , NH 2 , NHR 13 , N(R 13 ) 2 , NHC(0)R 13 , NR 13 C(0)R 13 , NHS(0) 2 R 13 , NR 13 S(0) 2 R 13 , NHC(0)OR 13 , NR 13 C(0)OR 13 , NHC(0)NH 2 , NHC(0)NHR 13 , NHC(0)N(R 13 ) 2 , NR 13 C(0)NHR 13 , NR 13 C(0)N(R 13 ) 2 , C(0)NH 2 , C(0)NHR 13 , C(0)N(R 13 ) 2 , C(0)NHOH, C(0)NHOR 13
  • R 13 is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkeny
  • R 14 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH 2 , S0 2 NH 2 , C(0)H, C(0)OH, OH, (O), CN, N 3 , N0 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, CI, Br or I; wherein each R 14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R 16 , OR 16 , OH, F, CI, Br, or I;
  • R 15 at each occurrence, is independently selected alkyl, wherein the R 15 alkyl is optionally substituted with one, two, three or four alkoxy;
  • R 16 at each occurrence, is independently selected alkyl, wherein the R 16 alkyl is optionally substituted with one, two, three or four alkoxy;
  • Another embodiment pertains to compounds having Formula (Ic) or Formula (Vc), and pharmaceutically acceptable salts thereof; wherein X 1 , X 2 , and X 3 are CH, or X 1 and X 3 are CH; and X 2 is CR 1 ; or X 2 and X 3 are CH; and X 1 is CR 1 ; or X 1 is CH; and X 2 and X 3 are CR 1 .
  • Another embodiment pertains to compounds having Formula (Ic) or Formula (Vc), and pharmaceutically acceptable salts thereof; wherein X 1 and X 3 are CH; and X 2 is N; or X 2 is CH; and X 1 and X 3 are N; X 2 and X 3 are CH; and X 1 is N; or X 1 is CH; X 2 is N; and X 3 is CR 1 ; or X 1 is CR 1 ; X 2 is N; and X 3 is CH; or X 1 is N; X 2 is CR 1 ; and X 3 is CH; or X 1 is N; X 2 is CR 1 ; and X 3 is CH; or X 1 is N; X 2 is CR 1 ; and X 3 is N.
  • Another embodiment pertains to compounds having Formula (Ic), and
  • R 2 is phenyl which is substituted at the para position with R 5 ; and R 5 is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7, 8-tetrahydrophthalazin- 1 (2H)-onyl, 5-fluorophthalazin- 1 (2H)-onyl, (Z)-3H- benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2- d][l,2,4]triazin-l(2H)-one, or isoindolin-l-onyl.
  • Still another embodiment pertains to compounds of Formula (Ic), which are

Abstract

Disclosed are compounds of formula (1c) which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed. Disclosed are compounds which inhibit the activity of ROCK, compositions containing the compounds and methods of treating diseases during which ROCK is expressed.

Description

NAMPT AND ROCK INHIBITORS
RELATED APPLICATION INFORMATION
This claims the benefit of U.S. Provisional Patent Application No. 61/413,722, filed on November 15, 2010, U.S. Provisional Patent Application Ser. No. 61/474,015, filed on April 11, 2011, and U.S. Provisional Patent Application Ser. No. 61/525,405, filed on August 19, 2011, the contents of each of which are herein incorporated by reference.
FIELD OF THE INVENTION
This invention pertains to compounds which inhibit the activity of NAMPT, compositions containing the compounds, and methods of treating diseases during which NAMPT is expressed. This invention also pertains to compounds which inhibit the activity of ROCK, compositions containing the compounds, and methods of treating diseases during which ROCK is expressed.
BACKGROUND OF THE INVENTION
NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays a critical role in many physiologically essential processes (Ziegkel, M. Eur. J. Biochem. 267,1550-1564, 2000). NAD is necessary for several signaling pathways including among others poly ADP- ribosylation in DNA repair, mono-ADP-ribosylation in both the immune system and G- protein-coupled signaling, and NAD is also required by sirtuins for their deacetylase activity (Garten, A. et al Trends in Endocrinology and Metabolism, 20, 130-138, 2008).
NAMPT (also known as pre-B-cell-colony-enhancing factor (PBEF) and visfatin) is an enzyme that catalyzes the phosphoribosylation of nicotinamide and is the rate-limiting enzyme in one of two pathways that salvage NAD.
D+ synthetase
Figure imgf000002_0001
Nicotinic acid mononucleotide
Nicotinic acid
(NA N)
Increasing evidence suggests that NAMPT inhibitors have potential as anticancer agents. Cancer cells have a higher basal turnover of NAD and also display higher energy requirements compared with normal cells. Additionally, increased NAMPT expression has been reported in colorectal cancer (Van Beijnum, J.R. et al Int. J. Cancer 101, 118-127, 2002) and NAMPT is involved in angiogenesis (Kim, S.R. et al. Biochem. Biophys. Res. Commun. 357, 150-156, 2007). Small-molecule inhibitors of NAMPT have been shown to cause depletion of intracellular NAD+ levels and ultimately induce tumor cell death (Hansen, CM et al. Anticancer Res. 20, 42111-4220, 2000) as well as inhibit tumor growth in xenograft models (Olese, U.H. et al. Mol Cancer Ther. 9, 1609-1617, 2010).
NAMPT inhibitors also have potential as therapeutic agents in inflammatory and metabolic disorders (Galli, M. et al Cancer Res. 70, 8-11, 2010). For example, NAMPT is the predominant enzyme in T and B lymphocytes. Selective inhibition of NAMPT leads to NAD+ depletion in lymphocytes blocking the expansion that accompanies autoimmune disease progression whereas cell types expressing the other NAD+ generating pathways might be spared. A small molecule NAMPT inhibitor (FK866) has been shown to selectively block proliferation and induce apoptosis of activated T cells and was efficacious in animal models of arthritis (collagen -induced arthritis) (Busso, N.et al. Plos One 3, e2267, 2008). FK866 ameliorated the manifestations of experimental autoimmune encephalomyelitis (EAE), a model of T-cell mediated autoimmune disorders. (Bruzzone, Set al. Plos One 4, e7897, 2009). NaMPT activity increases NF-kB transcriptional activity in human vascular endothelial cell, resulting in MMP-2 and MMP-9 activation, suggesting a role for NAMPT inhibitors in the prevention of inflammatory mediated complications of obesity and type 2 diabetes (Adya, R. et. Al. Diabetes Care, 31, 758-760, 2008).
Rho kinases (ROCKs), the first Rho effectors to be described, are serine/threonine kinases that are important in fundamental processes of cell migration, cell proliferation and cell survival. Abnormal activation of the Rho ROCK pathway has been observed in various disorders. Examples of disease states in which compounds with ROCK inhibition have potentially beneficial therapeutic effects due to their anti vasospasm activity includes cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension and atherosclerosis. This muscle relaxing property is also beneficial for treating asthma, male erectile dysfunctions, female sexual dysfunction, and over-active bladder syndrome. Injury to the adult vertebrate brain and spinal cord activates ROCKs, thereby inhibiting neurite growth and sprouting. Inhibition of ROCKs results in induction of new axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury). Inhibition of the Rho/ROCK pathway has also proved to be efficacious in other animal models of neurodegeneration like stroke, inflammatory and demyelinating diseases, Alzheimer's disease as well as for the treatment of pain. Rho ROCK pathway inhibitors therefore have potential for preventing
neurodegeneration and stimulating neuroregeneration in various neurological disorders, including spinal-cord injury, Alzheimer's disease, stroke, multiple sclerosis, amyotrophic lateral sclerosis, as well as for the treatment of pain. ROCK inhibitors have been shown to possess anti-inflammatory properties. Thus, compounds of the invention can be used as treatment for neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and inflammatory pain, as well as other diseases such as rheumatoid arthritis, osteoarthritis, asthma, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, Lupus, and inflammatory bowel disease. Since ROCK inhibitors reduce cell proliferation and cell migration, they could be useful in treating cancer and tumor metastasis. Further more, there is evidence suggesting that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in anti-viral and anti-bacterial applications. ROCK inhibitors are also useful for the treatment of insulin resistance and diabetes. Further, ROCK inhibitors have been shown to ameliorate progression of cystic fibrosis (Abstract S02.3, 8th World Congress on Inflammation, Copenhagen, Denmark, June 16-20, 2007).
In addition, Rho-associated coiled-coil forming protein kinases (ROCK)-l and -2, have been shown to enhance myosin light chain (MLC) phosphorylation by inhibiting MLC phosphatase as well as phosphorylating MLC. This results in the regulation of actin-myosin contraction. Recent reports have demonstrated that inhibition of ROCK results in disruption of inflammatory cell chemotaxis as well as inhibition of smooth muscle contraction in models of pulmonary inflammation associated with asthma. Therefore, the inhibitors of the
Rho ROCK pathway may be useful for the treatment of asthma.
SUMMARY OF THE INVENTION
One embodiment of this invention, therefore, pertains to compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT or ROCK, the compounds having Formula (Ic)
Figure imgf000004_0001
Formula (Ic);
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2,
C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein each R2 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4, OC(0)OR4, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH, C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4,
S02NH2, S02NHR4, S02N(R4)2, C(0)H, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5,
NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH,
C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R4, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 7 , OR 7 , SR 7 , S(0)R 7 , S02R 7 , C(0)R7, OC(0)R7, OC(0)OR7, NH2, NHR7, NHC(0)R7, NR7C(0)R7, NHS(0)2R7,
NR7S(0)2R7, NHC(0)OR7, NR7C(0)OR7, NHC(0)NH2, NHC(0)NHR7, NHC(0)N(R7)2, NR7C(0)NHR7, NR7C(0)N(R7)2, C(0)NH2, C(0)NHR7, C(0)N(R7)2, C(0)NHOH,
C(0)NHOR7, C(0)NHS02R7, C(0)NR7S02R7, S02NH2, S02NHR7, S02N(R7)2, C(0)H, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R4 aryl and heterocycyl is optionally substituted with one, two, three or four independently selected R8, OR8, SR8, S(0)R8, S02R8, C(0)R8, CO(0)R8, OC(0)R8, OC(0)OR8, NH2, NHR8, NHC(0)R8, NR8C(0)R8, NHS(0)2R8, NR8S(0)2R8, NHC(0)OR8, NR8C(0)OR8, NHC(0)NH2,
NHC(0)NHR8, NHC(0)N(R8)2, NR8C(0)NHR8, NR8C(0)N(R8)2, C(0)NH2, C(0)NHR8, C(0)N(R8)2, C(0)NHOH, C(0)NHOR8, C(0)NHS02R8, C(0)NR8S02R8, S02NH2,
S02NHR8, S02N(R8)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2,
S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R , NR1UC(0)R , NHS02R , NHC(0)OR , S02NH2, S02NHR1U, S02N(R1U)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R7, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R11, OR11, SR.11, S(0)Rn, S02Rn, NHR11, N(Rn)2, C(0)Rn, C(0)NH2, C(0)NHRn, C(0)N(Rn)2,
NHC(0)Rn, NRnC(0)Rn, NHS02Rn, NHC(0)ORn, S02NH2, S02NHRn, S02N(Rn)2, NHC(0)NH2, NHC(0)NHRn, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2,
NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R11, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R12, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I; wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy;
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. Another embodiment pertains to compounds having Formula (Vc), and p
Figure imgf000009_0001
(Vc);
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl, wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
Another embodiment pertains to compounds having Formula (Ic) or Formula (Vc), and pharmaceutically acceptable salts thereof; wherein X1, X2, and X3 are CH, or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1.
Another embodiment pertains to compounds having Formula (Ic) or Formula (Vc), and pharmaceutically acceptable salts thereof; wherein X1 and X3 are CH; and X2 is N; or X2 is CH; and X1 and X3 are N; X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. Another embodiment pertains to compounds having Formula (Ic), and
pharmaceutically acceptable salts thereof, wherein R2 is phenyl which is substituted at the para position with R5; and R5 is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7, 8-tetrahydrophthalazin- 1 (2H)-onyl, 5-fluorophthalazin- 1 (2H)-onyl, (Z)-3H- benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2- d][l,2,4]triazin-l(2H)-one, or isoindolin-l-onyl.
Still another embodiment pertains to compounds of Formula (Ic), which are
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(aminomethyl)benzyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxarnide;
N-(4- { [4-(furo[3,2-c]pyridin-4-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yfjcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(pyridin-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] -5-fluoro- 1 ,3-dmydro-2H-isoindole-2-carboxarnide; N- { 4- [(3,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yfjcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(thieno[3,2-c]pyridin-4-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(2,3-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4- [(3 -phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [4-(pyridazin-3-yl)piperazin-l-yl]carbonyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2,3-dihydro- 1 ,4-benzodioxin-5-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4-{ [l-(3-methylbutyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [4-(pyridin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-(4-{ [3-(2-oxopyrrolidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-methyl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(4-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-fluoro-5-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [4-(pyrazin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; 5-methoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [4-(pyrimidin-2 -yl)piperazin- 1 -yl] carbonyl } phenyl) -1,3 -dihydro-2H-isoindole- 2-carboxamide;
5-nitro-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-fluorophenyl)piperazin- 1 -yl] carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(2-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(3-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [4-(4-acetylphenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(2,3-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-chloro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4-phenylpiperazin-l-yl)carbonyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(6-aminohexyl)carbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide;
4- chloro-N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5- methoxy-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 ,3-benzodioxol-5-ylmethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-3-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridazin-3-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide; N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(3-fluorophenyl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl }phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3-butoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [2-(3,4-dihydroxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-propoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-furylmethyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide; N-(4- { [4-(2-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(3-hydroxy-2-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methylbutyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methyl-lH-indazol-5-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5-(trifluoromethyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(2,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
methyl 5-({4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl} amino)- 1H- indazole-3-carboxylate;
N-(4- { [2-(2-oxopyrrolidin- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide; N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(5-chloropyridin-2-yl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-indol-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro- 1 ,4-benzodioxin-6-ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(2-fluorobenzoyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(5-methoxy- lH-indol-3-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(2-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-propoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-4-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- [4 -( { 2- [4-(dimethylamino)phenyl] ethyl } carbamoyl)phenyl] -1,3 -dihydro -2H- isoindole-2-carboxamide; N-(4-{ [3-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-13-dmydro-2H-isoindole-2- carboxamide;
N-(4- { [(lR)-3-hydroxy- 1 -phenylpropyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-fluoro-4-methoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(l ,3-benzodioxol-5-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(2-methoxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-isopropoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-methoxypropyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [(2,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxamide; N-{ 4-[(2-phenoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [2-(4-hydroxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 1 - [(3S)-tetrahydrofuran-3 -yl] - 1 H-pyrazol-4-yl } carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(2-phenylethyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(methylthio)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-ethoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole -2-carboxamide; N- { 4- [(2-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 4-[(trifluoromethyl)thio]benzyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-fluorophenyl)pyrrolidin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(lH-irnidazol-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(3-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(hydroxymethyl)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-benzodioxol-5-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [( 1 -isopropyl- lH-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[methyl(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(thiomoφholin-4-ylcarbonyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(2-furoyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzylpiperidin-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(5-acetamido-2-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(3,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ 2-[3-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-( 1 H-imidazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [(1R)- 1 -(3-cyanophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [benzyl(2-hydroxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(4-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(pyridin-2-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyanomethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclohexylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[butyl(methyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [4-(dimemylamino)phenyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,4-dihydroisoquinolin-2(lH)-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro-lH-indol-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(phenylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [2-(diemylamino)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-hydroxy-2-phenylethyl)(methyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-aminophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1, 3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide; tert-butyl (1 - { 4-[( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl }piperidin-4- yl)carbamate;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 4- [3-chloro-5 -(trifluoromethyl)pyridin-2-yl]piperazin- 1 -yl } carbonyl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(cyclohexylmethyl)piperazin- 1 -yl]carbonyl} phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(3-chlorobenzyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(diethylcarbamoyl)piperidin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-hydroxyethyl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-hydroxy-6-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(dimethylarnino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-hydroxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5,6-dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(5-fluoropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopropylmethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(l,3,4,9-tetrahydro-2H-beta-carbolin-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tert-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({ 4-[4-(trifluoromethyl)phenyl]piperazin- 1 -yl}carbonyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,3-difluoropyrrolidin- 1 -yl)carbonyl]phenyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)- 1 -benzylpyrrolidin-3-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-carbamoylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopropylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(methylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(dimethylamino)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(pentan-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentan-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[( 1 ,3-dioxolan-2-ylmethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(4-fluorophenyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[( 1 -hydroxy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; Ν-{4-[(1 -phenyl- lH-pyrazol-4-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 2-[4-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2-methoxyethyl)(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(sec-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[bis(2-ethoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [butyl(ethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [isobutyl(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-carbamoylphenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)-2-(trifluoromethyl)pyrrolidin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [(2-methylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[ethyl(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[(2,6-dimethylmoφholin-4-yl)carbonyl]phenyl}-1 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(prop-2-yn- 1 -ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [isopropyl(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[isopropyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-cyanoethyl)(cyclopropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[emyl(isopropyl)carbamoyl]phenyl}-13-dmydro-2H-isoindole-2-carboxamide; N- { 4- [(3-fluoropyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -N-isopropyl-beta- alanine;
N-{4-[memyl(propyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide; 5,6-dimethoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [3-(4-chlorophenoxy)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethoxy)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-phenyl- 1 ,3-miazol-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
methyl 2- { [4-(propylcarbamoyl)phenyl] carbamoyl } isoindoline-5-carboxylate;
2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid;
5-amino-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-(aminomethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(2-hydroxy-2-methylpropanoyl)amino] -N-[4-(propylcarbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide; 5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(N,N-dimethylglycyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-[(methylsulfonyl)amino] -N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-[4-(propylcarbamoyl)phenyl]-13-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(4,4,4-trifluorobutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(4-phenylbutanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-methylpentanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(benzyloxy)acetyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenylpropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [N-(2-furoyl)glycyl] amino jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(2-thienyl)butanoyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(4-oxo-4-phenylbutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(N-benzoylglycyl)amino]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-{4-[(4-phenoxybutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(propionylamino)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(hexanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(heptanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pent-4-enoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(ethoxyacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2-methoxyethoxy)acetyl]amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyclopropylacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [3-(4-methylpiperazin-l-yl)propanoyl] amino jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5- carboxylate;
2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-cyclopentylethyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6- dihydropyridine- 1 (2H)-carboxylate;
N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -methyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 E)-5-phenylpent- 1 -en- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -propyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(l -benzyl- lH-pyrazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(2-hydroxyethyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-[6-(l -propyl- lH-pyrazol-4-yl)pyridin-3-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[l-(3-methylbutyl)-lH-pyrazol-4-yl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- [4 -(5 -phenylpentyl)phenyl] -1,3 -dihydro-2H-isoindole-2 -carboxamide;
N-[2-fluoro-4-(l -propyl- lH-pyrazol-4-yl)phenyl] -1, 3-dihydro-2H-isoindole -2- carboxamide;
N- { 2-fluoro-4- [ 1 -(3-methylbutyl)- 1 H-pyrazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetr ahydropyridin-4-yl)phenyl]- 1, 3-dihydro-2H-isoindo le-2- carboxamide;
N- { 4- [ 1 -(isopropylsulfonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(r-isobutyryl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(l'-benzoyl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-benzoylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(isopropylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(phenylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(benzoylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(butyrylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperazine- 1 - carboxylate;
N-[4-(4-propionylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[4-(cyclopropylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-butyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-(2-isobutyryl-2 -dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-benzoyl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[2-(3-methylbutyl)-2,3-dihydro-lH-isoindol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexyloxy)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[6-(4-chlorophenoxy)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(piperidin-4-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N,N'-hexane-l,6-diylbis(l,3-dihydro-2H-isoindole-2-carboxamide);
N-(4 -phenylbutyl) -1,3 -dihydro -2H-isoindole-2-carboxamide ;
ethyl 6-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]hexanoate;
N-hexyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-octyl-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [( 1 -methyl- 1 H-pyrazol-4-yl)amino] -6-oxohexyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[6-(memylamino)-6-oxohexyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N- { 6-0X0-6- [(3-phenylpropyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(3-methylbutyl)amino] -6-oxohexyl} -l,3-dihydro-2H-isoindole-2-carboxamide; N-(5 - { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl }pyridin-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 5-[(3-phenylpropyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{5-[(3-methylbutyl)carbamoyl]pyridin-2-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{5-[(3-phenylpropyl)carbamoyl]-l,3-thiazol-2-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 5-[(3-methylbutyl)carbamoyl]- 1 ,3-thiazol-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isoquinolin-4-yl)phenyl]-1 -dmydro-2H-isoindole-2-carboxamide; N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4, 5,6,7, 8-hexahydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(8-fluoro-4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
5-fluoro-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -5-(pyrrolidin- 1 -ylmethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-(morpholin-4-ylmethyl)-N-[4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-methoxy-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- [(4-methylpiperazin- 1 -yl)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-[4-(l -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-chloro-N- [4-( 1 -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-4,5-dihydro-3H-2,3-benzodiazepin-l-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -5 -(pyrrolidin- 1 -ylmethyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromemyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(4-methylpiperazin-l-yl)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide; N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } -5-(pyrrolidin- 1 - ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-[(l -methylpiperidin-4-yl)oxy] -N- [4-(4-oxo-3,4-dihydrophthalazin-l -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-{ [(3R)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-{ [(3S)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(azetidin- 1 -ylmethyl)-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
tert-butyl 4-{4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl}piperidine-l- carboxylate;
N-[4-(5-propyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(piperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 5-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-butyrylpiperidin-4-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(l -isobutyrylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(l -benzoylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[5-(3-methylbutyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-benzyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(5-chloropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(3-hydroxy-4-methoxyphenyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-oxopyrrolidin- 1 -yl)benzyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [(lS,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(l-hydroxycyclopropyl)methyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4-{6-[(1 -dmydro-2H-isoindol-2-ylcarbonyl)amino]-lH-benzimidazol-2- yl } piperazine- 1 -carboxylate;
N-[2-(piperazin- 1 -yl)- lH-benzimidazol-6-yl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] -5-vinyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-benzoylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(tetrahydrofuran-3-yl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- d]pyrimidine-6-carboxamide;
N-(4-{ [(3-phenylpropyl)amino]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- d]pyrimidine-6-carboxamide;
N-{4-[l-(4-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l -benzyl- 1,2,3, 6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(tetrahydrofuran-3-ylmethyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2S)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2R)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [( 1 S) -2-hydroxy- 1 -phenylethyl] amino } carbonyl)phenyl] -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [4-(2-methoxyethyl)piperazin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-2-(2-hydroxyethyl)piperidin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(propylamino)carbonyl]phenyl } -5-pyridin-3 -yl- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-4-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N5-(2-methoxyethyl)-N2-{4-[(propylamino)carbonyl]phenyl}-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N-(4-cyanophenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(trifluoromethyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4 - { [(tetrahydrofuran-3 -ylmethyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-pyridin-2-ylpiperazin-l-yl)carbonyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
5-( 1 ,2-dihydroxyethyl)-N- { 4- [(propylamino)carbonyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-5-cyano-l,3-dihydro-2H-isoindole-2- carboxamide; N l'-butyryl-r,2 3 6' etrahydro-3,4'-bipyridin-6-yl)-l,3-dmydro-2H-isoindole-2- carboxamide;
N-(r-isobutyryl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide; and
N-[2-(4-acetylpiperazin-l-yl)-lH-benzimidazol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(5-oxo-D-prolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -propionyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [ 1 -(2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(ethoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 - [(2-methoxyethoxy)acetyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl } phenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[l-(2-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(3-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(4-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(4-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(4-chlorobenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[3-(dimethylamino)benzoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[4-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(3-furoyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[l -(3-thienylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(lH-pyrrol-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(2,5 -dimethyl- 1 H-pyrrol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,3-thiazol-4-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(lH-pyrazol-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(3,5 -dimethyl- 1 ,2-oxazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-
2H-isoindole-2-carboxamide; N-[4-( 1 -isonicotinoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(pyridazin-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrimidin-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[3-(piperidin- 1 -yl)propanoyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(l'-benzoyl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [6-(benzoylamino)hexyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[(benzoylamino)methyl]benzyljcarbamoyl)phenyl]-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [4-(5-oxo-L-prolyl)piperazin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(5-oxo-D-prolyl)piperazin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[(l -acetylpiperidin-4-yl)carbonyl]piperazin-l -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(2-acetamidobenzoyl)piperazin-l -yljphenyl} -l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[4-(methylsulfonyl)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-butyrylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(4-isobutyrylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(2-methylbutanoyl)piperazin- 1 -yljphenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(3, 3, 3-trifluoropropanoyl)piperazin-l -yljphenyl }-l, 3-dihydro-2H-isoindole-
2-carboxamide; N-{4-[4-(methoxyacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[4-(tetrahydrofuran-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(cyclopentylacetyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(cyclohexylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(2-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(2-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(3-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[3-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {4-[4-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(3,4-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(3,5-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 4 - [(3 ,4 -dimethoxyphenyl) acetyl] piperazin- 1 -yl } phenyl)- 1 , 3 -dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(2-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(3-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[4-(lH-pyrrol-2-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(lH-pyrazol-5-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [4-(pyridin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(pyridin-3-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-isonicotinoylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyridazin-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrazin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrimidin-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(N,N-dimethyl-beta-alanyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-acetylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole -2-carboxamide;
N-{ 4-[4-(2-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(phenylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(l,3-thiazol-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(morpholin-4-ylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-phenylbutyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide; N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -oxo-2, 3-dihydro-lH-isoindol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)cyclohex-3 -en- 1 -yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[l -(3-methylbutyl)- lH-pyrazol-4-yl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[l -(2-phenylethyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N5-[2-(dimethylamino)ethyl]-N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {benzyl[3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(isobutoxycarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-bromo-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
methyl 4-{ [(5-cyano-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoate; N-(4- { (E)-[(benzyloxy)imino]methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-hydroxy-4-methylpentan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-aminopyrrolidin-l-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxarnide;
N-{6-[(3-methylbutyl)carbamoyl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(3-phenylpropyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2,5- dicarboxamide;
N-[4-({benzyl[3-(morpholin-4-yl)propyl] amino }methyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(pyridin-3-yl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-( 1 -methyl- lH-pyrazol-4-yl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-methoxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-hydroxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(aminomethyl)-N- { 4-[(cyclopentylacetyl)amino]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide; N-(4- { [(2S)- 1 -hydro xy-4-(memylthio)butan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2S,3S)-1 -hydroxy-3-methylpentan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S,3R)-1, 3-dihydroxybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xyhexan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-1 -hydro xypentan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S,2S)-2-hydroxycyclopentyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(lS,2R) -2-hydroxycyclopentyl] carb amoyl } phenyl) -1,3 -dihydro -2H-isoindole-
2-carboxamide;
N-(4- { [(2S)- 1 -cyclohexyl-3-hydroxypropan-2-yl] carbamoyl jphenyl)- 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ (2R)- 1 -hydroxy-3-[(4-methylbenzyl)thio]propan-2-yl }carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(IS)- 1 -(4-tert-butylphenyl)-2-hydroxyethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methoxy- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-memyl-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxarnide; N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-methylpentan-2-yl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[6-(benzoylamino)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(pyridin-3 -ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-(pyridin-4-yl)- 1 ,3 -dihydro-2H-isoindole-
2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(3-methylbutyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4-phenylbutyl)-l,3-dihydro-2H-isoindole-2-carboxamide; 5-(hydroxymethyl)-N-[l -(3-methylbutyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 5-[(3-methylbutyl)carbamoyl]pyrazin-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6-acetamidohexyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { ( 1 E) -3 - [benzyl(methyl) amino]prop- 1 -en- 1 -yl } phenyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(4-phenoxypiperidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(3-phenoxyazetidin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [benzyl(methyl)amino] methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide; N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(piperidin-l -yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1H- 1 ,2,3-triazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[2-(2-oxopyrrolidin-l-yl)ethyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(l-benzylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-phenylpropyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ l-[4-(morpholin-4-yl)benzyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-isobutyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(cyclopentylmethyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[l-(3-methoxypropyl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { 1 -[(2-memoxyemoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-{5-[l-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]pyridin-2-yl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-3-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4- { [(2 -methoxyethoxy) acetyl] amino jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(l'-isobutyryl-l',2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(l'-benzoyl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [4-(methylsulfonyl)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(ethoxyacetyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(cyclopentylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 6-[(2-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 6-[(3-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 6-[(4-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(2-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(3-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(2-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 6-[(3-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(4-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(2-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(3-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(4-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(3-cyanobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-cyanobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(6-{ [3-(dimemylamino)benzoyl]amino jhexyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [4-(dimethylamino)benzoyl]amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6-{ [3-(trifluoromethyl)benzoyl]amino jhexyl)- l,3-dihydro-2H-isoindole -2- carboxamide;
N-(6- { [4-(trifluoromemyl)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [3-(trifluoromethoxy)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,3-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,4-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,5-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(phenylacetyl)amino]hexylj-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(6- { [(3-fluorophenyl)acetyl]amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-2-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(ethoxyacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-(hydroxymethyl)-N-{4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]phenylj-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-{4-[(moφholin-4-ylacetyl)arnino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[6-(benzoylarrdno)hexyl]-13-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
4- fluoro-N-{6-[(pyridin-3-ylcarbonyl)arrdno]hexyl}-l,3-dmydro-2H-isoindole-2- carboxamide;
5- fluoro-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - l,3-dihydro-2H-isoindole-2- carboxamide; 5-methoxy-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [(pyridin-3 -ylcarbonyl)amino]hexyl } -5-(trifluoromethyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
4-cyano-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4- chloro-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5- cyano-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-chloro-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(pyridin-2-ylcarbonyl)amino]hexyl}-1 -dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(pyridin-2-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[l'-(tetrahydro-2H-pyran-4-ylcarbonyl)-l',2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-2,4'- bipyridin-5-yl}-13-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(2-hydro y-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ r-[(l-methylpyrrolidin-3-yl)carbonyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}- l,3-dihydro-2H-isoindole-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-2,4'- bipyridin-5 -yl } - 1 , 3 -dihydro-2H-isoindole-2 -carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(7 -oxo-7- { [(3R)-tetrahydrofuran-3-ylmethyl]aminojheptyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 7-oxo-7-[(tetrahydro-2H-pyran-4-ylmethyl)amino]heptyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(azetidin- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2-carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(morpholin-4-ylmethyl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{5-[(4-methylpiperazin-l-yl)methyl]-l,2,4-oxadiazol-3-yl Jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(5- { [(3-methylbutyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- {5-[(4-hydroxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl Jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-chlorobenzoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide; N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[l'-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { Γ- [( 1 -methylpyrrolidin-3-yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3 ,4'-bipyridin-6-yl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3,4'- bipyridin-6-yl } - 1 , 3 -dihydro-2H-isoindole-2 -carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [3-(dimethylamino)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [4-(2-aminoethyl)- lH-imidazol- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide; N-(4- { [(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl]carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-methoxy- 1 -phenylethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ [(4S)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ [(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}carbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino } -2-oxoethyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(3- {benzyl[3-(morpholin-4-yl)propyl] amino } -3-oxopropyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2R)-butan-2-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methyl- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(6-bromo-2-oxoquinolin-l(2H)-yl)butyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[6-(3-acetylphenyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(morpholin-4-ylacetyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide; N-[Γ-(moφholin-4-ylacetyl)-1^2^3^6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(2- { (4-fluorobenzyl)[4-(pyridin-3-yl)benzyl]amino } - 1 ,3-miazol-5-yl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2 -benzyl- 1 ,3-miazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(7 - { benzyl [3 -(morpholin-4-yl)propyl] amino } -7 -oxoheptyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)sulfamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(cyclopentylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- {4-[(l, 3-thiazol-5-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1R) -3 -hydroxy- 1 -phenylpropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(4-methylphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(l ,3-dihydroxypropan-2-yl)carbamoyl]phenylj - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3 -dihydro -2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2R)-l-hydroxy-3-methylbutan-2-yl]carbamoyljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2-(4-methylpiperazin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyljcarbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(4-hydroxybutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; 5-cyano-N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl}phenyl)-1 -dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(3-furylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- {4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(2-furoyl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yljcarbonyl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-tetrahydrofuran-2-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(ethylsulfonyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- {4-[(tetrahydro furan-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(lR)-2-hydroxy- 1 -phenylethyljcarbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2S)-1 -hydro xybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2,3-dihydroxypropyl)carbamoyl]phenylj - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(pyridin-2-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(l -hydroxy-4-methylpentan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide; N-(5- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl }pyridin-2-yl)- 1 ,3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.3]hept-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.4]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,9-diazaspiro[5.5]undec-3-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- {benzyl[3-(morpholin-4-yl)propyl] amino } -4-oxobutyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-phenylbutyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino }ethyl)phenyl]- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-acetyl-N-{4-[(cyclopentylacetyl)arnino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide; 5-cyano-N- { 4-[(3-methylbutyl)sulfamoyl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -hydroxy ethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(butyrylamino)phenyl] -5-cyano- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3-methoxybenzyl)sulfonyl]amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2, 8 -diazaspiro [4.5] dec-2 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2,7 -diazaspiro [4.5] dec-7 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenylj-l,3- dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 8 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(2-oxa-7-azaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[6-(3-acetylphenyl)-4-(3-hydroxypropyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-(acetamidomethyl)-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{5-[2-(2-chlorobenzyl)-l,3-thiazol-4-yl]-2-thienyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-fluorophenyl)butyl]-5-(hydroxymethyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl] methyl } carbamoyl)phenyl] - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydro-2H-pyran-4-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l-(tetrahydro-2H^yran-4-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(2-hydroxypropan-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl {4-[(13-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzyl}carbamate;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(methoxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(5- { [(tetrahydrofuran-2-ylmethyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- {5-[(4-methoxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl Jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(5- { [4-(2-methoxyethyl)piperazin- 1 -yl]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl]- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [ 1 -(morpholin-4 -yl)cyclopentyl] methyl } carbamoyl)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-pentanoylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(l-acetylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butyrylpiperidin-4-yl)oxy]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-4-yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dmydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[( 1 -acetylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [( 1 -isobutyrylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [ 1 -(3-methylbutanoyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(methoxyacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopropylacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6 - { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl] oxy } pyridin-3 -yl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopentylacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl (2- { 4- [( 1 ,3-dihydro-2H-isoindol-2- ylc arbonyl) amino] phenyl } ethyl)c arb amate ;
N-(4-{ l-[(2R)-tetrahydrofuran-2-ylcarbonyl] -1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-cyano-N- { 4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N- { 4- [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(3 -phenylpropanoyl)pyrrolidin- 3 -yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- [4 -( { 1 - [(4-methoxyphenyl) acetyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)pyrrolidin-3 -yl] oxy } phenyl) -1,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-benzoylpyrrolidin-3-yl)oxy]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N- [4 -( { 1 - [( 1 -methylcyclopropyl)carbonyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -acetylpyrrolidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine- 2-carboxamide;
N-(4- { [ 1 -(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethoxyacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ 1-[(1 -methylpiperidin-4-yl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetrahydrofuran-3-ylcarbonyl]-l,2,3,6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
tert-butyl [( 1 - { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } azetidin-3- yl)methyl]carbamate;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(morpholin-4-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2-methoxyethoxy)acetyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(2,3-dimethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide; N-(4-{ [l-(2-methylbutanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2,2-dimethylpropanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tricyclo[3.3.1.1~3,7~]dec-l-ylacetyl)azetidin-3-yl]oxy}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [(4-methoxycyclohexyl)carbonyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [4-(acetylamino)phenyl] sulfonyl } amino)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(propylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-propylphenyl)sulfonyl]amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(butylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine-2- carboxamide;
N-{4-[({ [(lS,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-l- yl]methyl } sulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(ethylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(benzylsulfonyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-fluorophenyl)sulfonyl] amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(thiophen-2-ylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,6-diazaspiro[3.5]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l-(tetrahydrofuran-3-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(Ν,Ν-dimethylglycyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l-en-l-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] amino } cyclohex- 1 -en- 1 - yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(4,4-difluorocyclohexyl)carbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(piperidin- 1 -ylsulfonyl)phenyl]- 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
5-fluoro-N-(4-{ [l-(l,3-thiazol-2-yl)propan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4,4-difluorocyclohexyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- lH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5-fluoro- l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl- l-(morpholin-4-yl)propan-2-yl] carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N- { 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-D- phenylalanin amide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl}phenyl)-5- fluoro- 1, 3 -dihydro-2H-isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl} -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide; 5-fluoro-N- { 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(5-methyl-lH-pyrazol-l-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-chloro-lH-pyrazol-l-yl)ethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-5,7- dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yljcarbonyl)phenyl]-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-carbamoylbenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 ,7-dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
Nalpha-{4-[(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-ylcarbonyl)amino]benzoyl}-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5,7-dihydro-6H-pyrrolo [3 ,4- b]pyridine-6-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(4,5,6,7-tetrahydro-lH-indazol-5-ylcarbamoyl)phenyl]-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [(3-methyl- 1 ,2-oxazol-5-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(lH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[methyl(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrazol-3-yl)methyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- {4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(l -methoxybutan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } -5-fluoro- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl} -5-fluoro- l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(5-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(pyridin-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cycloprop yle thy 1] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4-{ [l-(l-methylcyclopropyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4- [(thiophen-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(4-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(2S)- 1 -methoxypropan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrrol-2-yl)methyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyljphenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -amino- 1 -oxobutan-2-yl] carbamoyl }phenyl)-5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(l -methoxypropan-2-yl)carbamoyl]phenylj -l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl]-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-2-methylbutyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5-fluoro-1 -dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N- { 4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l-cyanoethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [(3-methyl- 1 ,2-oxazol-5-yl)methyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(1 -methyl- lH-pyrazol-3-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [4-(dimemylarrdno)butyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide; N-(4-{ [l-(l,3-thiazol-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -methoxybutan-2-yl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-{4-[(4-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(2-ethoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{ 4-[( 1 -cyanocyclopropyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(5-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(4-methyl-l,3-thiazol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-{4-[(2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(lR)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(thiophen-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(lS)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [( 1 -methyl- 1 H-pyrrol-2-yl)methyl] carbamoyl }phenyl)-5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-cyanoethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide; N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[methyl(propyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b] pyridine-6-carboxamide;
methyl 1 - { 4- [( 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } azetidine-3-carboxylate;
N-(4- { 3 - [(3-methylbutyl)carbamoyl] azetidin- 1 -yl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydrofuran-2-ylmethyl)carbamoyl] azetidin- 1 -yljphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [3 -(benzylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c] pyridine-2-carboxamide;
N- { 4- [3 -(cyclopentylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 3-[(cyclopentylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{3-[(2-methoxyethyl)carbamoyl]azetidin-l -yljphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopentylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-2-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [ 1 -(pyrrolidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4,4-difluorocyclohexyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-memyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({2-[(dimethylamino)methyl]benzyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,3-oxazol-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(furan-2-yl)-2-(pyrrolidin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydrofuran-3-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- {4-[l-(morpholin-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(4-fluorobenzyl)(3-methylbutanoyl)amino]butyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6H-furo[2',3':2,3]cyclobuta[l,2- c]quinolin-6-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[7-chloro-l-(2-hydroxyethyl)-3-oxo-l,3-dihydrocyclobuta[c]quinolin-4(2H)- yl]butyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[( 1 -acetylpiperidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butanoylpiperidin-3 -yl)oxy] phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4 - { [ 1 -(methoxyacetyl)piperidin-3 -yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(cyclopentylacetyl)piperidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [3-(3,5 -dimethyl- IH-pyrazol- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [ 1 -( 1 ,3 -thiazol-2-yl)ethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(2,2-difluoroethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-4-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -L- phenylalanin amide;
N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)-3,3-dimethyl- 1 -(methylamino)- 1 -oxobutan-2-yl]carbamoyl jphenyl)- 1 ,3 dihydro-2H-isoindole-2-carboxamide;
N-[4-(thiophen-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(5-methyl- IH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3-methyl- IH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-3-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(acetylamino)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -methoxybutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pyrimidin-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-( 1 H-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-methylbutyl] carbamoyl jphenyl)- 1, 3-dihydro-2H-iso indole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]butylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}butyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(propan-2-yloxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(4,4,4-trifluorobutanoyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(3-ethoxypropanoyl)amino]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(1 -acetylpiperidin-4-yl)carbonyl] amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(ethoxyacetyl)amino]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [(tetrahydrofuran-2-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2-carboxamide; N-{7-oxo-7-[(3-phenylpropyl)amino]heptyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(bicyclo[2.2 ]hept-2-ylacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 ,3-thiazol-5-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(4-0X0-4, 5,6,7-tetrahydro-l-benzofuran-3-yl)carbonyl] amino jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {2-[(3-methylbutanoyl)amino]ethyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{2-[(4-methylpentanoyl)amino]ethyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(ethoxy acetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(2- { [(2-methoxyethoxy)acetyl] amino } ethyl)phenyl]- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-2-ylcarbonyl) amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(cyclopentylcarbonyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(cyclopentylacetyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[2-(benzoylamino)emyl]phenyl}-l,3-dmydro-2H-isoindole-2-carboxamide;
N-(4-{2-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]ethyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydro-2H-pyran-4 -ylacetyl)amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-3 -ylacetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 -propanoylazetidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide; N-(4- { [ 1 -(2,2-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-ethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(pent-4-ynoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)azetidin-3 -yl]oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethylglycyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethyl-beta-alanyl)azetidin-3 -yljoxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrrolidin- 1 -ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(pyrrolidin-l-yl)propanoyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [3-(piperidin- 1 -yl)propanoyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[(4-methylpiperazin- 1 -yl)acetyl] azetidin-3-yl }oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(4-methylpiperazin-l-yl)propanoyl]azetidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopropylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopentylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(2-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3,3-dimethylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(butylsulfonyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylsulfonyl)piperidin-4-yl] oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(4-fluorophenyl)sulfonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propan-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(benzylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-2-methylbutanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(4,4-difluorocyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-l,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-D-prolyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylpropanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpentanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-ethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(l H-pyrrol-2-ylcarbonyl)piperidin-4-yl] oxy jphenyl) -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(l,2 -oxazol-5 -ylcarbonyl)piperidin-4-yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridazin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrazin-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(piperidin-l-yl)propanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[3-(4-methylpiperazin- 1 -yl)propanoyl]piperidin-4-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
benzyl trans-3-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl)amino]cyclobutanecarboxylate; N-[4-(4- { [(4-methylpiperazin- 1 -yl)acetyl] amino jcyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(benzoylamino)cyclohex- 1 -en- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 -methylpiperidin-4-yl)carbonyl] amino jcyclohex- 1 -en-1 -yl)phenylj- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(1,1 -dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3R)-tetrahydrofuran-3-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3S)-tetrahydrofuran-3 -ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-2-methylbutanoyl]amino jcyclohex- 1 -en-1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 3 - [(3 -methylbu tanoyl) amino] oxetan-3 -yl } phenyl) - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
tert-butyl 4-({4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } sulfonyl)piperidine- 1 -carboxylate;
N-{ 4-[4-(propylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(2-methoxyethyl)carbamoyl]piperidin- 1 -yl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(cyclopentylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(l ,4-dioxan-2-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [4-(cyclopentylcarbamoyl)piperidin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)piperidin-l -yljphenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[4-(morpholin-4-ylcarbonyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[4-(cyclopropylcarbamoyl)piperidin-l-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-hydroxy-2-methylpropyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(butan-2-ylcarbamoyl)piperidin- 1 -yljphenyl } -1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yljphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{(4R)-4-[(2-methylpropanoyl)amino]cyclohex-l -en-1 -yljphenyl)- 1,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { (4S)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzoylazetidin-3-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-benzoylazetidin-3-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[trans-3-(benzylcarbamoyl)cyclobutyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{trans-3-[(2-phenylethyl)carbamoyl]cyclobutylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { trans-3- [(3-phenylpropyl)carbamoyl] cyclobutyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide; N-(4- { 1 -[(2-methyl- 1 ,3-oxazol-4-yl)carbonyl]- 1 ,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(furan-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-3-(furan-2-yl)prop-2-enoyl] -1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,3-oxazol-5-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3,3,3-trifluoropropanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,5 -dimethyl- 1 H-pyrazol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methoxycyclohexyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2,3-dimethylbutanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2,2-difluorocyclopropyl)carbonyl] -1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(lH-pyrazol-5-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tert-butoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-l, 2,4-triazol- 1 -yl)propanoyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-ethoxypropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-hydroxy-3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-pyrrol- l-yl)propanoyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylcyclopropyl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methylpropoxy)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l-methylprolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(2-hydro y-2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -hydroxycyclopropyl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l - { [1 -(methoxymethyl)cyclopropyl]carbonyl } - 1 ,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(methylsulfonyl)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -acetyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-{ 4- [1 -(eye loprop ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-4-methylpent-2-enoyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-methoxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopent- 1 -en- 1 -ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 - dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(thiophen-3-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -propanoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2,2-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { 1 - [( 1 -methyl- 1 H-pyrrol-2-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,2-dimethylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(4-methylhexanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-dimethylcyclopropyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-5-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(cyclobutylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } -1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(piperidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[2-(pyrrolidin- 1 -yl)propanoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2-methoxyethoxy)acetyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -(trans-4- { [(2 -methoxyethoxy) acetyl] amino } cyclohexyl)phenyl] -1,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } eye lohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3R)-1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [(3R)- 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl] oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ (3R)- 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3R)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(bicyclo[2.2.1]hept-2-ylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(2-methylpropanoyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(2-methylpropanoyl)amino]cyclohexyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(cyclohexylcarbonyl)amino]cyclohexyljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(cyclohexylcarbonyl)aminojcyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { trans-4- [(cyclopropylacetyl)amino]cyclohexyl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {cis-4-[(cyclopropylacetyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(cyclopentylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l -en-1 -yljphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; and pharmaceutically acceptable salts thereof.
Still another embodiment pertains to compounds of Formula (Ic), which are
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamo yljphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonylj- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 -dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Still another embodiment pertains to compounds of Formula (Ic), which are
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Another embodiment pertains to a composition for treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal- cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases,
Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis, said composition comprising an excipient and a therapeutically effective amount of a compound of Formula (Ic), or pharmaceutically acceptable salts thereof.
Another embodiment pertains to a composition for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said composition comprising an excipient and a therapeutically effective amount of a compound of Formula (Ic), or pharmaceutically acceptable salts thereof.
Another embodiment pertains to a method of treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal- cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis, in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound of Formula (Ic), or pharmaceutically acceptable salts thereof.
Another embodiment pertains to a method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage;
autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound of Formula (Ic), or pharmaceutically acceptable salts thereof.
Another embodiment pertains to a method of treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal- cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of Formula (Ic), or pharmaceutically acceptable salts thereof; and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Another embodiment pertains to a method of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia or spleen cancer in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of Formula (Ic), or pharmaceutically acceptable salts thereof; and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent. DETAILED DESCRIPTION OF THE INVENTION
This detailed description is intended only to acquaint others skilled in the art with Applicants' invention, its principles, and its practical application so that others skilled in the art may adapt and apply the invention in its numerous forms, as they may be best suited to the requirements of a particular use. This description and its specific examples are intended for purposes of illustration only. This invention, therefore, is not limited to the embodiments described in this patent application, and may be variously modified.
Abbreviations and Definitions
Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning and scope of the terms should be clear, however, in the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. In this application, the use of "or" means "and/or" unless stated otherwise. Furthermore, the use of the term "including", as well as other forms, such as "includes" and "included", is not limiting. With reference to the use of the words "comprise" or "comprises" or "comprising" in this patent application (including the claims), Applicants note that unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted inclusively, rather than exclusively, and that Applicants intend each of those words to be so interpreted in construing this patent application, including the claims below. For a variable that occurs more than one time in any substituent or in the compound of the invention or any other formulae herein, its definition on each occurrence is independent of its definition at every other occurrence. Combinations of substituents are permissible only if such combinations result in stable compounds. Stable compounds are compounds which can be isolated in a useful degree of purity from a reaction mixture.
It is meant to be understood that proper valences are maintained for all combinations herein, that monovalent moieties having more than one atom are attached through their left ends, and that divalent moieties are drawn from left to right.
As used in the specification and the appended claims, unless specified to the contrary, the following terms have the meaning indicated:
The term "alkyl" (alone or in combination with another term(s)) means a straight-or branched-chain saturated hydrocarbyl substituent typically containing from 1 to about 10 carbon atoms; or in another embodiment, from 1 to about 8 carbon atoms; in another embodiment, from 1 to about 6 carbon atoms; and in another embodiment, from 1 to about 4 carbon atoms. Examples of such substituents include methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, sec -butyl, tert-butyl, pentyl, iso-amyl, and hexyl and the like. The term "alkenyl" (alone or in combination with another term(s)) means a straight- or branched-chain hydrocarbyl substituent containing one or more double bonds and typically from 2 to about 10 carbon atoms; or in another embodiment, from 2 to about 8 carbon atoms; in another embodiment, from 2 to about 6 carbon atoms; and in another embodiment, from 2 to about 4 carbon atoms. Examples of such substituents include ethenyl (vinyl), 2-propenyl, 3-propenyl, 1,4-pentadienyl, 1,4-butadienyl, 1-butenyl, 2-butenyl, and 3-butenyl and the like.
The term "alkynyl" (alone or in combination with another term(s)) means a straight- or branched-chain hydrocarbyl substituent containing one or more triple bonds and typically from 2 to about 10 carbon atoms; or in another embodiment, from 2 to about 8 carbon atoms; in another embodiment, from 2 to about 6 carbon atoms; and in another embodiment, from 2 to about 4 carbon atoms. Examples of such substituents include ethynyl, 2-propynyl, 3- propynyl, 2-butynyl, and 3-butynyl and the like.
The term "carbocyclyl" (alone or in combination with another term(s)) means a saturated cyclic (i.e., "cycloalkyl"), partially saturated cyclic (i.e., "cycloalkenyl"), or completely unsaturated (i.e., "aryl") hydrocarbyl substituent containing from 3 to 14 carbon ring atoms ("ring atoms" are the atoms bound together to form the ring or rings of a cyclic substituent). A carbocyclyl may be a single-ring (monocyclic) or polycyclic ring structure.
A carbocyclyl may be a single ring structure, which typically contains from 3 to 8 ring atoms, more typically from 3 to 6 ring atoms, and even more typically 5 to 6 ring atoms. Examples of such single-ring carbocyclyls include cyclopropyl (cyclopropanyl), cyclobutyl (cyclobutanyl), cyclopentyl (cyclopentanyl), cyclopentenyl, cyclopentadienyl, cyclohexyl (cyclohexanyl), cyclohexenyl, cyclohexadienyl, and phenyl. A carbocyclyl may alternatively be polycyclic (i.e., may contain more than one ring). Examples of polycyclic carbocyclyls include bridged, fused, and spirocyclic carbocyclyls. In a spirocyclic carbocyclyl, one atom is common to two different rings. An example of a spirocyclic carbocyclyl is spiropentanyl. In a bridged carbocyclyl, the rings share at least two common non-adjacent atoms. Examples of bridged carbocyclyls include bicyclo[2.2.1]heptanyl, bicyclo[2.2.1]hept-2-enyl, and adamantanyl. In a fused-ring carbocyclyl system, two or more rings may be fused together, such that two rings share one common bond. Examples of two- or three-fused ring carbocyclyls include naphthalenyl, tetrahydronaphthalenyl (tetralinyl), indenyl, indanyl (dihydroindenyl), anthracenyl, phenanthrenyl, and decalinyl.
The term "cycloalkyl" (alone or in combination with another term(s)) means a saturated cyclic hydrocarbyl substituent containing from 3 to 14 carbon ring atoms. A cycloalkyl may be a single carbon ring, which typically contains from 3 to 8 carbon ring atoms and more typically from 3 to 6 ring atoms. Examples of single-ring cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. A cycloalkyl may alternatively be polycyclic or contain more than one ring. Examples of polycyclic cycloalkyls include bridged, fused, and spirocyclic carbocyclyls. In a bridged cycloalkyl, the rings share at least two common non-adjacent atoms. Examples of bridged cycloalkyls include
bicyclo[2.2.1]heptanyl and adamantanyl.
The term "aryl" (alone or in combination with another term(s)) means an aromatic carbocyclyl containing from 6 to 14 carbon ring atoms. An aryl may be monocyclic or polycyclic (i.e., may contain more than one ring). In the case of polycyclic aromatic rings, only one ring in the polycyclic system is required to be unsaturated while the remaining ring(s) may be saturated, partially saturated or unsaturated. Examples of aryls include phenyl, naphthalenyl, indenyl, 2,3-dihydroindenyl, indanyl, and tetrahydronapthyl.
In some instances, the number of carbon atoms in a hydrocarbyl substituent (e.g., alkyl, alkenyl, alkynyl, or cycloalkyl) is indicated by the prefix "Cx-Cy-", wherein x is the minimum and y is the maximum number of carbon atoms in the substituent. Thus, for example, "Ci-C6-alkyl" refers to an alkyl substituent containing from 1 to 6 carbon atoms. Illustrating further, C3-C8-cycloalkyl means a saturated hydrocarbyl ring containing from 3 to 8 carbon ring atoms.
The term "hydrogen" (alone or in combination with another term(s)) means a hydrogen radical, and may be depicted as -H.
The term "hydroxy" (alone or in combination with another term(s)) means -OH.
The term "carboxy" (alone or in combination with another term(s)) means -C(0)-OH. The term "amino" (alone or in combination with another term(s)) means -NH2.
The term "halogen" or "halo" (alone or in combination with another term(s)) means a fluorine radical (which may be depicted as -F), chlorine radical (which may be depicted as - CI), bromine radical (which may be depicted as -Br), or iodine radical (which may be depicted as -I).
If a substituent is described as being "substituted", a non-hydrogen radical is in the place of hydrogen radical on a carbon or nitrogen of the substituent. Thus, for example, a substituted alkyl substituent is an alkyl substituent in which at least one non-hydrogen radical is in the place of a hydrogen radical on the alkyl substituent. To illustrate, monofluoroalkyl is alkyl substituted with a fluoro radical, and difluoroalkyl is alkyl substituted with two fluoro radicals. It should be recognized that if there are more than one substitution on a substituent, each non-hydrogen radical may be identical or different (unless otherwise stated).
If a substituent is described as being "optionally substituted", the substituent may be either (1) not substituted or (2) substituted. If a substituent is described as being optionally substituted with up to a particular number of non-hydrogen radicals, that substituent may be either (1) not substituted; or (2) substituted by up to that particular number of non-hydrogen radicals or by up to the maximum number of substitutable positions on the substituent, whichever is less. Thus, for example, if a substituent is described as a heteroaryl optionally substituted with up to 3 non-hydrogen radicals, then any heteroaryl with less than 3 substitutable positions would be optionally substituted by up to only as many non-hydrogen radicals as the heteroaryl has substitutable positions. To illustrate, tetrazolyl (which has only one substitutable position) would be optionally substituted with up to one non-hydrogen radical. To illustrate further, if an amino nitrogen is described as being optionally substituted with up to 2 non-hydrogen radicals, then a primary amino nitrogen will be optionally substituted with up to 2 non-hydrogen radicals, whereas a secondary amino nitrogen will be optionally substituted with up to only 1 non-hydrogen radical.
This patent application uses the terms "substituent" and "radical" interchangeably. The prefix "halo" indicates that the substituent to which the prefix is attached is substituted with one or more independently selected halogen radicals. For example, haloalkyl means an alkyl substituent in which at least one hydrogen radical is replaced with a halogen radical. Examples of haloalkyls include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, and 1,1, 1-trifluoroethyl. It should be recognized that if a substituent is substituted by more than one halogen radical, those halogen radicals may be identical or different (unless otherwise stated).
The prefix "perhalo" indicates that every hydrogen radical on the substituent to which the prefix is attached is replaced with independently selected halogen radicals, i.e., each hydrogen radical on the substituent is replaced with a halogen radical. If all the halogen radicals are identical, the prefix typically will identify the halogen radical. Thus, for example, the term "perfluoro" means that every hydrogen radical on the substituent to which the prefix is attached is substituted with a fluorine radical. To illustrate, the term "perfluoroalkyl" means an alkyl substituent wherein a fluorine radical is in the place of each hydrogen radical.
The term "carbonyl" (alone or in combination with another term(s)) means -C(O)-. The term "aminocarbonyl" (alone or in combination with another term(s)) means -
C(0)-NH2.
The term "oxo" (alone or in combination with another term(s)) means (=0).
The term "oxy" (alone or in combination with another term(s)) means an ether substituent, and may be depicted as -0-.
The term "alkylhydroxy" (alone or in combination with another term(s)) means - alkyl-OH.
The term "alkylamino" (alone or in combination with another term(s)) means -alkyl-
NH2.
The term "alkyloxy" (alone or in combination with another term(s)) means an alkylether substituent, i.e., -O-alkyl. Examples of such a substituent include methoxy (-0- CH3), ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy. The term "alkylcarbonyl" (alone or in combination with another term(s)) means - C(0)-alkyl.
The term "aminoalkylcarbonyl" (alone or in combination with another term(s)) means -C(0)-alkyl-NH2.
The term "alkyloxycarbonyl" (alone or in combination with another term(s)) means -
C(0)-0-alkyl.
The term "carbocyclylcarbonyl" (alone or in combination with another term(s)) means -C(0)-carbocyclyl.
Similarly, the term "heterocyclylcarbonyl" (alone or in combination with another term(s)) means -C(0)-heterocyclyl.
The term "carbocyclylalkylcarbonyl" (alone or in combination with another term(s)) means -C(0)-alkyl-carbocyclyl.
Similarly, the term "heterocyclylalkylcarbonyl" (alone or in combination with another term(s)) means -C(0)-alkyl-heterocyclyl.
The term "carbocyclyloxycarbonyl" (alone or in combination with another term(s)) means -C(0)-0-carbocyclyl.
The term "carbocyclylalkyloxycarbonyl" (alone or in combination with another term(s)) means -C(0)-0-alkyl-carbocyclyl.
The term "thio" or "thia" (alone or in combination with another term(s)) means a thiaether substituent, i.e. , an ether substituent wherein a divalent sulfur atom is in the place of the ether oxygen atom. Such a substituent may be depicted as -S-. This, for example, "alkyl- thio-alkyl" means alkyl-S-alkyl (alkyl-sulfanyl-alkyl).
The term "thiol" or "sulfhydryl" (alone or in combination with another term(s)) means a sulfhydryl substituent, and may be depicted as -SH.
The term "(thiocarbonyl)" (alone or in combination with another term(s)) means a carbonyl wherein the oxygen atom has been replaced with a sulfur. Such a substituent may be depicted as -C(S)-.
The term "sulfonyl" (alone or in combination with another term(s)) means -S(0)2-. The term "aminosulfonyl" (alone or in combination with another term(s)) means - S(0)2-NH2.
The term "sulfinyl" or "sulfoxido" (alone or in combination with another term(s)) means -S(O)-.
The term "heterocyclyl" (alone or in combination with another term(s)) means a saturated (i.e., "heterocycloalkyl"), partially saturated (i.e., "heterocycloalkenyl"), or completely unsaturated (i.e., "heteroaryl") ring structure containing a total of 3 to 20 ring atoms. At least one of the ring atoms is a heteroatom (i.e. , oxygen, nitrogen, or sulfur), with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen, and sulfur. A heterocyclyl may be a single-ring (monocyclic) or polycyclic ring structure.
A heterocyclyl may be a single ring, which typically contains from 3 to 7 ring atoms, more typically from 3 to 6 ring atoms, and even more typically 5 to 6 ring atoms. Examples of single-ring heterocyclyls include 1,2,3,6-tetrahydropyridine, thiomorpholinyl, tetrahydropyranyl, furanyl, dihydrofuranyl, tetrahydrofuranyl, thiophenyl (thiofuranyl), dihydrothiophenyl, tetrahydrothiophenyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidin-2-onyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, triazolyl, tetrazolyl, oxazolyl, oxazolidinyl, isoxazolidinyl, isoxazolyl, thiazolyl, isothiazolyl, thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazolidinyl, thiodiazolyl, oxadiazolyl (including 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl (furazanyl), or 1,3,4-oxadiazolyl), oxatriazolyl (including 1,2,3,4-oxatriazolyl or 1,2,3,5-oxatriazolyl), dioxazolyl (including 1,2,3-dioxazolyl, 1,2,4-dioxazolyl, 1,3,2-dioxazolyl, or 1,3,4-dioxazolyl), oxathiazolyl, oxathiolyl, oxathiolanyl, pyranyl, dihydropyranyl, thiopyranyl, tetrahydrothiopyranyl, pyridinyl (azinyl), piperidinyl, diazinyl (including pyridazinyl (1,2-diazinyl), pyrimidinyl
(1,3-diazinyl), or pyrazinyl (1,4-diazinyl)), piperazinyl, pyrrolidin-2-only, triazinyl (including 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,2,3-triazinyl)), oxazinyl (including 1,2-oxazinyl, 1,3- oxazinyl, or 1 ,4-oxazinyl)), oxathiazinyl (including 1,2,3-oxathiazinyl, 1,2,4-oxathiazinyl, 1,2,5-oxathiazinyl, or 1,2,6-oxathiazinyl)), oxadiazinyl (including 1,2,3-oxadiazinyl, 1,2,4- oxadiazinyl, 1,4,2-oxadiazinyl, or 1,3, 5 -oxadiazinyl)), morpholinyl, azepinyl, oxepinyl, thiepinyl, diazepinyl, thiomorpholinyl, tetrahydrothiophenyl 1,1-dioxidyl, tetrahydro-2/f- thiopyranyl, 1,1-dioxidyl, oxetanyl, azetidinyl, thiazolyl, azepanyl, azepan-2-onyl, and dioxolayl (including 1,3-dioxolanyl).
A heterocyclyl may alternatively be polycyclic (i.e., may contain more than one ring). Examples of polycyclic heterocyclyls include bridged, fused, and spirocyclic heterocyclyls. In a spirocyclic heterocyclyl, one atom is common to two different rings. In a bridged heterocyclyl, the rings share at least two common non-adjacent atoms. In a fused-ring heterocyclyl, two or more rings may be fused together, such that two rings share one common bond. Examples of fused ring heterocyclyls containing two, three or four rings include hexahydro-furo[3,4-c]pyrrole, hexahydro-furo[3,4-b]pyrrole, octahydro-pyrrolo[3,4- b]pyridine, octahydro-pyrrolo[3,4-c]pyridine, (3aR,6aR)-5-methyl-octahydro-pyrrolo[3,4- b]pyrrole, (3aR,6aR)-octahydro-pyrrolo[3,4-b]pyrrole, 6-methyl-2,6-diaza- bicyclo[3.2.0]heptane, (3aS,6aR)-2-methyl-octahydro-pyrrolo[3,4-c]pyrrole, decahydro- [l,5]naphthyridine, 2,3-dihydrobenzofuranyl, 2,3,4,9-tetrahydro-lH-pyrido[3,4-b]indolyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, isoindolin-l-onyl, phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7, 8-tetrahydrophthalazin-l(2H)-onyl,
fluorophthalazin- 1 (2H)-onyl, (Z)-3H-benzo [d] [1 ,2]diazepin-4(5H)-onyl, (trifluoromethyl)phthalazin- 1 (2H)-onyl, pyrrolo [ 1 ,2-d] [ 1 ,2,4] triazin- 1 (2H)-onyl, 1 ,2,3,4- tetrahydroisoquinolinyl, 2,3 -dihydrobenzo [b] [ 1 ,4] dioxinyl, 5,6,7,8 -tetrahydrophthalazin- l(2H)-onyl, 5,6,7,8-tetrahydro-[l,2,4]triazolo[4,3-a]pyrazinyl, 5,6,7,8-tetrahydroirnidazo[l,5- a]pyrazinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, indolizinyl, pyranopyrrolyl, 4H- quinolizinyl, purinyl, naphthyridinyl, pyridopyridinyl (including pyrido[3,4-b]-pyridinyl, pyrido[3,2-b]-pyridinyl, or pyrido[4,3-b]-pyridinyl), pteridinyl, 4,5,6,7-tetrahydro-indolyl, 5,6,7, 8-tetrahydroimidazo[l,5-a]pyrazinyl, 6,7-dihydropyrrolo[3,4-d]pyrimidinyl, 6,7- dihydropyrrolo[3,4-b]pyridinyl, 2,3-dihydropyrrolo[3,4-c]pyridinyl, 6,7-dihydrobenzofuran- 4(5H)-onyl, indolinyl, benzo[d][l,3]dioxolyl, isoquinolinyl, indolyl, quinolin-2(lH)-onyl, benzo[d]imidazolyl, l,2,3,4-tetrahydrocyclobuta[c]quinolinyl, 1,2- dihydrocyclobuta[c]quinolin-3(4H)-onyl, and 3,3a,4,4a-tetrahydro-2/f- furo[2',3':2,3]cyclobuta[l,2-c]quinolin-5(6//)-onyl. Other examples of fused-ring heterocyclyls include benzo-fused heterocyclyls, such as benzimidazolyl,
benzo[d][l,3]dioxolyl, indolyl, isoindolyl (isobenzazolyl, pseudoisoindolyl), indoleninyl (pseudoindolyl), isoindazolyl (benzpyrazolyl), benzazinyl (including quinolinyl (1- benzazinyl) or isoquinolinyl (2 -benzazinyl)), phthalazinyl, quinoxalinyl, quinazolinyl, benzodiazinyl (including cinnolinyl (1,2-benzodiazinyl) or quinazolinyl (1,3-benzodiazinyl)), benzopyranyl (including chromanyl or isochromanyl), benzoxazinyl (including 1,3,2- benzoxazinyl, 1,4,2-benzoxazinyl, 2,3,1 -benzoxazinyl, or 3,1,4-benzoxazinyl), benzisoxazinyl (including 1,2-benzisoxazinyl or 1,4-benzisoxazinyl), isoindolin-l-onyl, 2,3- dihydrobenzo[b][l,4]dioxinyl, 1,2,3,4-tetrahydroisoquinolinyl, quinolin-2(lH)-onyl, benzo[d]imidazolyl, 2,3,4,9-tetrahydro-pyrido[3,4-b]indolyl, 1,2,3,4- tetrahydrocyclobuta[c]quinolinyl, l,2-dihydrocyclobuta[c]quinolin-3(4H)-onyl, and 3,3a,4,4a- tetrahydro-2/f-furo[2',3':2,3]cyclobuta[l,2-c]quinolin-5(6//)-onyl. Examples of spirocyclic heterocyclyls include l,4-dioxa-8-azaspiro[4.5]decanyl, 2-oxa-6-aza-spiro[3.3]heptanyl, bicyclo[2.2.1]heptan-2-only, 6-oxa-l-aza-spiro[3.3]heptanyl, 2-oxa-7-aza-spiro[3.5]nonanyl, 2-oxa-6-aza-spiro[3.5]nonanyl, 2-oxa-5-aza-spiro[3.5]nonanyl, 2-oxa-6-aza-spiro[3.4]octanyl, 2-oxa-5-aza-spiro[3.4]octanyl, 2,7-diazaspiro[3.5]nonane, l,4-dioxa-8-azaspiro[4.5]decanyl, 2-oxa-9-azaspiro [5.5]undecanyl, 2,9-diazaspiro [5.5]undecanyl, 2, 8-diazaspiro [5.5]undecanyl, l-oxa-8-azaspiro[5.5]undecanyl, l,8-diazaspiro[5.5]undecanyl, 3,9-diazaspiro[5.5]undecanyl, 1 -oxa-4, 8 -diazaspiro [5.5] undecanyl, 1 , 8 -diazaspiro [4.6]undecanyl, 1 -oxa- 8 - azaspiro[4.5]decanyl, 2,7-diazaspiro[4.5]decanyl, l,8-diazaspiro[4.5]decanyl, 2,8- diazaspiro[4.5]decanyl, 2,6-diazaspiro[4.5]decanyl, l,4-dioxaspiro[4.5]decanyl, 1,7- diazaspiro[4.4]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2,5-diazaspiro[3.5]nonanyl, 2,6- diazaspiro [3.5]nonanyl, l,7-diazaspiro[3.5]nonanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 1,6- diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.4]octanyl, 6-oxa-2-azaspiro[3.4]octanyl, 5-oxa-2- azaspiro[3.4]octanyl, and 2,6-diazaspiro[3.3]heptanyl. The term "heterocycloalkyl" (alone or in combination with another term(s)) means a saturated heterocyclyl. Examples of heterocycloalkyls include piperidine, tetrahydropyranyl, piperazinyl, morpholinyl, azepan-2-oneyl, pyrrolidinyl, 1,3-dioxolanyl, tetrahydrofuranyl, pyrrolidin-2-onyl, oxetanyl, azetidinyl, 2-oxa-9-azaspiro[5.5]undecanyl, 2,9- diazaspiro[5.5]undecanyl, 2,8-diazaspiro[5.5]undecanyl, l-oxa-8-azaspiro[5.5]undecanyl, 1,8- diazaspiro [5.5]undecanyl, 3,9-diazaspiro [5.5]undecanyl, 1 -oxa-4, 8-diazaspiro [5.5]undecanyl, l,8-diazaspiro[4.6]undecanyl, l-oxa-8-azaspiro[4.5]decanyl, 2,7-diazaspiro[4.5]decanyl, 1,8- diazaspiro[4.5]decanyl, 2,8-diazaspiro[4.5]decanyl, 2,6-diazaspiro[4.5]decanyl, 1,4- dioxaspiro[4.5]decanyl, l,7-diazaspiro[4.4]nonanyl, 2,7-diazaspiro[4.4]nonanyl, 2,5- diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.5]nonanyl, l,7-diazaspiro[3.5]nonanyl, 6-oxa-2- azaspiro[3.5]nonanyl, l ,6-diazaspiro[3.5]nonanyl, 2,6-diazaspiro[3.4]octanyl, 6-oxa-2- azaspiro[3.4]octanyl, 5-oxa-2-azaspiro[3.4]octanyl, bicyclo[2.2.1]heptan-2-onyl, l,4-dioxa-8- azaspiro[4.5]decanyl, 2,7-diazaspiro[3.5]nonanyl and 2,6-diazaspiro[3.3]heptanyl.
The term "heteroaryl" (alone or in combination with another term(s)) means an aromatic heterocyclyl containing from 5 to 14 ring atoms. A heteroaryl may be monocyclic or polycyclic (i.e., may contain more than one ring). In the case of a polycyclic heteroaryl, only one heterocyclyl ring in the polycyclic system is required to be unsaturated while the remaining ring(s) may be saturated, partially saturated or unsaturated. Examples of heteroaryl substituents include: 6-membered ring substituents such as pyridyl, pyrazyl, pyrrolyl, isoxazolyl, 1,2,3-triazolyl, pyrimidinyl, pyridazinyl, and 1,3,5-, 1 ,2,4- or 1,2,3-triazinyl; 5- membered ring substituents such as imidazyl, furanyl, thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1 ,2,3-, 1,2,4-, 1,2,5-, and 1,3,4-, oxadiazolyl and isothiazolyl; 6/5- membered fused ring substituents such as indolyl, benzothiofuranyl, benzisoxazolyl, benzoxazolyl, purinyl, 4,5,6,7-tetrahydro-indolyl, furo[3,2-c]pyridinyl, pyrrolo[l,2- d] [l,2,4]triazin-l(2H)-onyl, thieno[3,2-c]pyridinyl, 5,6,7,8-tetrahydroimidazo[l,5- a]pyrazinyl, benzo[d]imidazolyl, 6,7-dihydro-pyrrolo[3,4-d]pyrimidinyl, 6,7-dihydro- pyrrolo[3,4-b]pyridinyl, 2,3-dihydro-pyrrolo[3,4-c]pyridinyl, 5,6,7,8-tetrahydroirnidazo[l,5- a]pyrazinyl, 6,7-dihydrobenzofuran-4(5H)-onyl, 6,7-dihydrobenzofuran-4(5H)-onyl, and indolyl; 6/6-membered fused rings such as benzopyranyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, benzoxazinyl, 5,6,7, 8-tetrahydrophthalazin-l(2H)-onyl, phthalazin- l(2H)-onyl, isoquinolin-l(2H)-onyl, and quinolin-2(lH)-onyl; 6/5/6 membered rings such as 2,3,4,9-tettahydro-lH-pyrido[3,4-b]indolyl, and l,2-dihydrocyclobuta[c]quinolin-3(4H)-onyl; and 6/6/4/5 membered rings such as 2,3,4,9-tetrahydro-pyrido[3,4-b]indolyl.
A prefix attached to a multi-component substituent only applies to the first component. To illustrate, the term "alkylcycloalkyl" contains two components: alkyl and cycloalkyl. Thus, the Ci-C6- prefix on Ci-C6-alkylcycloalkyl means that the alkyl component of the alkylcycloalkyl contains from 1 to 6 carbon atoms; the Ci-C6-prefix does not describe the cycloalkyl component. To illustrate further, the prefix "halo" on haloalkyloxyalkyl indicates that only the alkyloxy component of the alkyloxyalkyl substituent is substituted with one or more halogen radicals. If halogen substitution may alternatively or additionally occur on the alkyl component, the substituent would instead be described as "halogen-substituted alkyloxyalkyl" rather than "haloalkyloxyalkyl." And finally, if the halogen substitution may only occur on the alkyl component, the substituent would instead be described as
"alkyloxyhaloalkyl."
The terms "treat", "treating" and "treatment" refer to a method of alleviating or abrogating a disease and/or its attendant symptoms.
The terms "prevent", "preventing" and "prevention" refer to a method of preventing the onset of a disease and/or its attendant symptoms or barring a subject from acquiring a disease. As used herein, "prevent", "preventing" and "prevention" also include delaying the onset of a disease and/or its attendant symptoms and reducing a subject's risk of acquiring a disease.
The term "therapeutically effective amount" refers to that amount of the compound being administered sufficient to prevent development of or alleviate to some extent one or more of the symptoms of the condition or disorder being treated.
The term "modulate" refers to the ability of a compound to increase or decrease the function, or activity, of a kinase. "Modulation", as used herein in its various forms, is intended to encompass antagonism, agonism, partial antagonism and/or partial agonism of the activity associated with kinase. Kinase inhibitors are compounds that, e.g., bind to, partially or totally block stimulation, decrease, prevent, delay activation, inactivate, desensitize, or down regulate signal transduction. Kinase activators are compounds that, e.g., bind to, stimulate, increase, open, activate, facilitate, enhance activation, sensitize or up regulate signal transduction.
The term "composition" as used herein is intended to encompass a product comprising the specified ingredients in the specified amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By "pharmaceutically acceptable" it is meant the carrier, diluent or excipient must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
The "subject" is defined herein to include animals such as mammals, including, but not limited to, primates (e.g., humans), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice and the like. In preferred embodiments, the subject is a human.
Isotope Enriched or Labeled Compounds
Compounds of the invention can exist in isotope-labeled or -enriched form containing one or more atoms having an atomic mass or mass number different from the atomic mass or mass number most abundantly found in nature. Isotopes can be radioactive or non-radioactive isotopes. Isotopes of atoms such as hydrogen, carbon, phosphorous, sulfur, fluorine, chlorine, and iodine include, but are not limited to, 2H, 3H, 13C, 14C, 15N, 180, 32P, 35S, 18F, 36C1, and 125I. Compounds that contain other isotopes of these and/or other atoms are within the scope of this invention.
In another embodiment, the isotope-labeled compounds contain deuterium (2H), tritium (3H) or 14C isotopes. Isotope-labeled compounds of this invention can be prepared by the general methods well known to persons having ordinary skill in the art. Such isotope- labeled compounds can be conveniently prepared by carrying out the procedures disclosed in the Examples disclosed herein and Schemes by substituting a readily available isotope-labeled reagent for a non-labeled reagent. In some instances, compounds may be treated with isotope-labeled reagents to exchange a normal atom with its isotope, for example, hydrogen for deuterium can be exchanged by the action of a deuteric acid such as D2S04/D20. In addition to the above, relevant procedures and intermediates are disclosed, for instance, in Lizondo, J et al., Drugs Fut, 21(11), 1116 (1996); Brickner, S J et al, J Med Chem, 39(3), 673 (1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); PCT publications
WO1997010223, WO2005099353, WO1995007271, WO2006008754; US Patent Nos. 7538189; 7534814; 7531685; 7528131 ; 7521421 ; 7514068; 7511013; and US Patent Application Publication Nos. 20090137457; 20090131485; 20090131363; 20090118238; 20090111840; 20090105338; 20090105307; 20090105147; 20090093422; 20090088416; and 20090082471, the methods are hereby incorporated by reference.
The isotope-labeled compounds of the invention may be used as standards to determine the effectiveness of Bcl-2 inhibitors in binding assays. Isotope containing compounds have been used in pharmaceutical research to investigate the in vivo metabolic fate of the compounds by evaluation of the mechanism of action and metabolic pathway of the nonisotope-labeled parent compound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are important in the design of safe, effective therapeutic drugs, either because the in vivo active compound administered to the patient or because the metabolites produced from the parent compound prove to be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London, 1985; Kato et al., J. Labelled Comp. Radiopharmaceut. , 36(10):927-932 (1995); Kushner et al., Can. J. Physiol.
Pharmacol, 77, 79-88 (1999).
In addition, non-radio active isotope containing drugs, such as deuterated drugs called "heavy drugs," can be used for the treatment of diseases and conditions related to Bcl-2 activity. Increasing the amount of an isotope present in a compound above its natural abundance is called enrichment. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol %. Replacement of up to about 15% of normal atom with a heavy isotope has been effected and maintained for a period of days to weeks in mammals, including rodents and dogs, with minimal observed adverse effects (Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770; Thomson J F, Ann. New York Acad. Sci 1960 84: 736; Czakja D M et al., Am. J. Physiol. 1961 201 : 357). Acute replacement of as high as 15%- 23% in human fluids with deuterium was found not to cause toxicity (Blagojevic N et al. in "Dosimetry & Treatment Planning for Neutron Capture Therapy", Zamenhof R, Solares G and Harling O Eds. 1994. Advanced Medical Publishing, Madison Wis. pp.125-134; Diabetes Metab. 23: 251 (1997)).
Stable isotope labeling of a drug can alter its physico-chemical properties such as pKa and lipid solubility. These effects and alterations can affect the pharmacodynamic response of the drug molecule if the isotopic substitution affects a region involved in a ligand-receptor interaction. While some of the physical properties of a stable isotope-labeled molecule are different from those of the unlabeled one, the chemical and biological properties are the same, with one important exception: because of the increased mass of the heavy isotope, any bond involving the heavy isotope and another atom will be stronger than the same bond between the light isotope and that atom. Accordingly, the incorporation of an isotope at a site of metabolism or enzymatic transformation will slow said reactions potentially altering the pharmacokinetic profile or efficacy relative to the non-isotopic compound.
Compounds
Suitable groups for X1, X2, X3, and R2 in compounds of Formula (I) are independently selected. The described embodiments of the present invention may be combined. Such combination is contemplated and within the scope of the present invention. For example, it is contemplated that embodiments for any of X1, X2, X3, and R2 can be combined with embodiments defined for any other of X1, X2, X3, and R2.
Embodiments of Formula (I)
One embodiment of this invention, therefore, pertains to compounds or
pharmaceutically acceptable salts, which are useful as inhibitors of NAMPT, the compounds having Formula (I)
Figure imgf000107_0001
Formula (I),
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4, OC(0)OR4, NH2, NHR4, N(R4)2, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH, C(0)NHOR4,
C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each phenyl is optionally substituted at the para position with one independently selected R5,
OCH2CH2CH2CH2CH2CH3, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5,
NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5,
C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each phenyl is optionally substituted with one F; wherein each heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH,
C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein R2 is not 4- methylphenyl;
R3 is alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R6, OR6, SR6,
S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2,
S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R4 is alkyl, alkenyl, alkynyl, aryl or heterocyclyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R7, OR7, SR7, S(0)R7, S02R7, C(0)R7, CO(0)R7, OC(0)R7, OC(0)OR7, NH2, NHR7, N(R7)2, NHC(0)R7, NR7C(0)R7, NHS(0)2R7, NR7S(0)2R7, NHC(0)OR7, NR7C(0)OR7, NHC(0)NH2,
NHC(0)NHR7, NHC(0)N(R7)2, NR7C(0)NHR7, NR7C(0)N(R7)2, C(0)NH2, C(0)NHR7, C(0)N(R7)2, C(0)NHOH, C(0)NHOR7, C(0)NHS02R7, C(0)NR7S02R7, S02NH2,
S02NHR7, S02N(R7)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each aryl and heterocycyl is optionally substituted with one or more independently selected R8, OR8, SR8, S(0)R8, S02R8, C(0)R8, CO(0)R8, OC(0)R8, OC(0)OR8, NH2, NHR8, N(R8)2, NHC(0)R8, NR8C(0)R8, NHS(0)2R8, NR8S(0)2R8, NHC(0)OR8, NR8C(0)OR8, NHC(0)NH2, NHC(0)NHR8, NHC(0)N(R8)2, NR8C(0)NHR8, NR8C(0)N(R8)2, C(0)NH2, C(0)NHR8, C(0)N(R8)2, C(0)NHOH, C(0)NHOR8,
C(0)NHS02R8, C(0)NR8S02R8, S02NH2, S02NHR8, S02N(R8)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10,
SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R7 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R11, OR11, SR11, S(0)Rn, S02Rn, NHR11, N(Rn)2, C(0)Rn, C(0)NH2, C(0)NHRn, C(0)N(Rn)2, NHC(0)Rn, NRnC(0)Rn, NHS02Rn, NHC(0)ORn, S02NH2, S02NHRn, S02N(Rn)2, NHC(0)NH2, NHC(0)NHRn, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2, NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, or aryl;
R10 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R11 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R12 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one or more independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13 is alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, cycloalkyl, or cycloalkenyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, CO(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14,
S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R , C(0)NR13S02R , S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; and
R15 is alkyl.
In one embodiment of Formula (I), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is
CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N. In another embodiment of Formula (I), X1, X2, and X3 are CH. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (I), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is N.
In another embodiment of Formula (I), R1 is R3, OR3, C(0)OR3, C(0)NH2,
C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (I), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2,
N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), R1 is C(0)NH2. In another embodiment of Formula (I), R1 is F. In another embodiment of Formula (I), R1 is CI. In another embodiment of Formula (I), R1 is Br. In another embodiment of Formula (I), R1 is CN. In another embodiment of Formula (I), R^s NH2. In another embodiment of Formula (I), R1 is N02. In another embodiment of Formula (I), R1 is CF3. In another embodiment of Formula (I), R1 is C(0)OH.
In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 and X3 are
CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another
- I l l - embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R s NH2. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (I), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2,
N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and RHs NH2. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (I), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is OR3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is C(0)OR 3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (I), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH.
In one embodiment of Formula (I), X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R2 is alkyl, phenyl, heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R4, OR4, C(0)R4, CO(0)R4, NHC(0)R4, C(0)NHR4, F, CI, Br or I; each phenyl is optionally substituted at the para position with one independently selected R5, OCH2CH2CH2CH2CH2CH3, C(0)R5, NHR5, NHC(0)R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, or CF3; wherein each phenyl is optionally substituted with one F; wherein each heterocyclyl is optionally substituted with one or more independently selected R5, C(0)R5, NHC(0)R5, C(0)NHR5, F, CI, Br or I; wherein R2 is not 4-methylphenyl;
R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, OH, F, CI, Br or I;
R4 is alkyl, aryl or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R7, F, CI, Br or I; wherein each aryl and heterocycyl is optionally substituted with one or more independently selected R8, C(0)R8, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, C(0)NH2, C(0)OH, OH, CN, CF3, F, CI, Br or I;
R6 is alkyl or heterocyclyl;
R7 is aryl;
R8 is alkyl, aryl, or heterocyclyl;
R9 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OCH3, or aryl;
wherein the cyclic moieties represented by R 3 , R 5 , R 6 , R 7 , R 8 , and R 9 are optionally substituted with one or more independently selected R13, OR13S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13 is alkyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, or pyrrolidin-2-onyl, wherein each alkyl is optionally substituted with one or more independently selected R14, OR14, NH2, OH, F, CI, Br or I; wherein each aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, C(0)R15, CN, CF3, F, CI, Br or I;
R14 is alkyl, aryl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OH, F, CI, Br or I; and
R15 is alkyl.
Still another embodiment pertains to compounds having Formula (I), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 1 11, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201 , 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391 , 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (II)
In another aspect, the present invention provides compounds of Formula (II)
Figure imgf000117_0001
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (I); and R2 is phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein the phenyl, heterocyclyl, cycloalkyl, and cycloalkenyl are optionally substituted as described herein for Formula (I).
In one embodiment of Formula (II), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N. In another embodiment of Formula (II), X1, X2, and X3 are CH. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (II), X1 and
X 3 are CH; and X 2 is CR 1. In another embodiment of Formula (II), X 2 and X 3 are CH; and X 1 is CR1. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (II), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is N.
In another embodiment of Formula (II), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (II), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), R1 is C(0)NH2 In another embodiment of Formula (II), R1 is F. In another embodiment of Formula (II), R1 is CI. In another embodiment of Formula (II), R1 is Br. In another embodiment of Formula (II), R1 is CN. In another embodiment of Formula (II), RHs NH2. In another embodiment of Formula (II), R1 is N02. In another embodiment of Formula (II), R1 is CF3. In another embodiment of Formula (II), R1 is C(0)OH.
In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. Γη another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and RHs NH2. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (II), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (II), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is C(0)OR 3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are
CR1; and R1 is CI. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is NH2. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (II), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH.
In one embodiment of Formula (II),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R2 is phenyl, or heterocyclyl; wherein each phenyl is optionally substituted at the para position with one independently selected R5, OCH2CH2CH2CH2CH2CH3, C(0)R5, NHR5, NHC(0)R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, or CF3; wherein each phenyl is optionally substituted with one F; wherein each heterocyclyl is optionally substituted with one or more independently selected R5, C(0)R5, NHC(0)R5, C(0)NHR5, F, CI, Br or I; wherein R2 is not 4-methylphenyl;
R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, OH, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, 0 OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, C(0)NH2, C(0)OH, OH, CN, CF3, F, CI, Br or
I;
R6 is alkyl or heterocyclyl;
R9 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OCH3, or aryl;
wherein the cyclic moieties represented by R3, R5, R6, and R9 are optionally substituted with one or more independently selected R13, OR13S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13 is alkyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, or pyrrolidin-2-onyl, wherein each alkyl is optionally substituted with one or more independently selected R14, OR14, NH2, OH, F, CI, Br or I; wherein each aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, C(0)R15, CN, CF3, F, CI, Br or I;
R14 is alkyl, aryl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OH, F, CI, Br or I; and
R15 is alkyl.
Still another embodiment pertains to compounds having Formula (II), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 452, 453, 454, 455, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (III)
In another aspect, the present invention provides compounds of Formula (III)
Figure imgf000123_0001
(in);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (I); and Rx is as described herein for Formula (I) when R2 is phenyl.
In one embodiment of Formula (III), X1, X2, and X3 are CH; or X1 and X3 are CH; and
X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N. In another embodiment of Formula (III), X1, X2, and X3 are CH. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (III), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is N.
In another embodiment of Formula (III), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (III), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), R1 is C(0)NH2. In another embodiment of Formula (III), R1 is F. In another embodiment of Formula (III), R1 is CI. In another embodiment of Formula (III), R1 is Br. In another embodiment of Formula (III), R1 is CN. In another embodiment of Formula (III), RHs NH2. In another embodiment of Formula (III), R1 is N02. In another embodiment of Formula (III), R1 is CF3. In another embodiment of Formula (III), R1 is C(0)OH.
In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and RHs NH2. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (III), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R^s NH2. Γη another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (III), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and RHs NH2. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (III), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH.
In another embodiment of Formula (III), Rx is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-l(2H)-onyl, 5-fluorophthalazin-l(2H)- onyl, (Z)-3H-benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, or pyrrolo [ 1 ,2-d] [ 1 ,2,4] triazin- 1 (2H)-one.
In one embodiment of Formula (III),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I,
CN, NH2, N02, CF3, or C(0)OH;
Rx is R5, OCH2CH2CH2CH2CH2CH3, C(0)R5, NHR5, NHC(0)R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CF3 or F;
R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, OH, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, C(0)NH2, C(0)OH, OH, CN, CF3, F, CI, Br or
I;
R6 is alkyl or heterocyclyl;
R9 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OCH3, or aryl;
wherein the cyclic moieties represented by R3, R5, R6, and R9 are optionally substituted with one or more independently selected R13, OR13S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13 is alkyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, or pyrrolidin-2-onyl, wherein each alkyl is optionally substituted with one or more independently selected R14, OR14, NH2, OH, F, CI, Br or I; wherein each aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R , OR , C(0)R , CN, CF3, F, CI, Br or I;
R14 is alkyl, aryl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OH, F, CI, Br or I; and
R15 is alkyl.
Still another embodiment pertains to compounds having Formula (III), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 1 11, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 330, 331, 332, 333, 336, 337, 338, 339, 340, 341 , 342, 343, 348, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, , 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 547, 548, 549, 550, 551, 552, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (TV)
In
Figure imgf000128_0001
(IV); or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (I).
In one embodiment of Formula (IV), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N. In another embodiment of Formula (IV), X1, X2, and X3 are CH. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (IV), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is N.
In another embodiment of Formula (IV), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IV), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), R1 is C(0)NH2. In another embodiment of Formula (IV), R1 is F. In another embodiment of Formula (IV), R1 is CI. In another embodiment of Formula (IV), R1 is Br. In another embodiment of Formula (IV), R1 is CN. In another embodiment of Formula (IV), RHs NH2. Γη another embodiment of Formula (IV), R1 is N02. In another embodiment of Formula (IV), R1 is CF3. In another embodiment of Formula (IV), R1 is C(0)OH.
In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and RHs NH2. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (IV), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X2 and X3 are CHj and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and RHs NH2. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (IV), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (IV), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH.
In one embodiment of Formula (IV),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I,
CN, NH2, N02, CF3, or C(0)OH;
R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, OH, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9,
OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, C(0)NH2, C(0)OH, OH, CN, CF3, F, CI, Br or
I;
R6 is alkyl or heterocyclyl;
R9 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OCH3, or aryl;
wherein the cyclic moieties represented by R3, R5, R6, and R9 are optionally substituted with one or more independently selected R13, OR13S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13 is alkyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, or pyrrolidin-2-onyl, wherein each alkyl is optionally substituted with one or more independently selected R14, OR14, NH2, OH, F, CI, Br or I; wherein each aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, C(0)R15, CN, CF3, F, CI, Br or I;
R14 is alkyl, aryl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OH, F, CI, Br or I; and
R15 is alkyl.
Still another embodiment pertains to compounds having Formula (IV), which include
Examples 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, and pharmaceutically acceptable salts thereof. Embodiments of Formula (V)
In another aspect, the present invention provides compounds of Formula (V)
Figure imgf000134_0001
(V);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (I).
In one embodiment of Formula (V), X1, X2, and X3 are CH; or X1 and X3 are CH; and
X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N. In another embodiment of Formula (V), X1, X2, and X3 are CH. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (V), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is N.
In another embodiment of Formula (V), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (V), R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), R1 is C(0)NH2 In another embodiment of Formula (V), R1 is F. In another embodiment of Formula (V), R1 is CI. In another embodiment of Formula (V), R1 is Br. In another embodiment of Formula (V), R1 is CN. In another embodiment of Formula (V), R^s NH2. In another embodiment of Formula (V), R1 is N02. In another embodiment of Formula (V), R1 is CF3. In another embodiment of Formula (V), R1 is C(0)OH.
In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (V), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (V), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH.
In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is OR3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is C(0)OR 3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and RHs NH2. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is N02. Γη another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (V), X1 is CH; and X2 and X3 are CR^ and R1 is C(0)OH.
In one embodiment of Formula (V),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, OH, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, C(0)NH2, C(0)OH, OH, CN, CF3, F, CI, Br or
I;
R6 is alkyl or heterocyclyl;
R9 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OCH3, or aryl;
wherein the cyclic moieties represented by R3, R5, R6, and R9 are optionally substituted with one or more independently selected R13, OR13S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13 is alkyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, or pyrrolidin-2-onyl, wherein each alkyl is optionally substituted with one or more independently selected R14, OR14, NH2, OH, F, CI, Br or I; wherein each aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, C(0)R15, CN, CF3, F, CI, Br or I;
R14 is alkyl, aryl, or cycloalkyl; wherein each alkyl is optionally substituted with one or more independently selected OH, F, CI, Br or I; and
R15 is alkyl. Still another embodiment pertains to compounds having Formula (V), which include
Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 176, 177, 178, 179, 180, 181, 182, 184, 185, 186, 187, 188, 189, 190, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 209, 210, 211, 213, 214, 215, 216, 217, 218, 219, 220, 221, 223, 224, 225, 226, 227, 228, 230, 231, 232, 234, 235, 236, 237, 239, 240, 243, 245, 246, 248, 249, 250, 251, 252, 253, 254, 256, 257, 258, 259, 260, 265, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 373, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 424, 425, 426, 427, 430, 431, 434, 435, 436, 437, 438, 439, 440, 441, 442, 445, 449, 450, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (la)
One embodiment of this invention, therefore, pertains to compounds or
pharmaceutically acceptable salts, which are useful as inhibitors of NAMPT, the compounds having Formula (la)
Figure imgf000139_0001
Formula (la);
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein each R2 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4,
OC(0)OR4, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH, C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OCH2CH2CH2CH2CH2CH3, SR5, S(0)R5, S02R5, C(0)R5,
CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5,
NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein R2 is not 4-methylphenyl;
R3 is alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R6, OR6, SR6,
S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2,
NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2,
S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; R4 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R7, OR7, SR7, S(0)R7, S02R7, C(0)R7, OC(0)R7, OC(0)OR7, NH2, NHR7, NHC(0)R7,
NR7C(0)R7, NHS(0)2R7, NR7S(0)2R7, NHC(0)OR7, NR7C(0)OR7, NHC(0)NH2,
NHC(0)NHR7, NHC(0)N(R7)2, NR7C(0)NHR7, NR7C(0)N(R7)2, C(0)NH2, C(0)NHR7, C(0)N(R7)2, C(0)NHOH, C(0)NHOR7, C(0)NHS02R7, C(0)NR7S02R7, S02NH2,
S02NHR7, S02N(R7)2, C(0)H, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R4 aryl and heterocycyl is optionally substituted with one or more independently selected R8, OR8, SR8, S(0)R8, S02R8, C(0)R8, CO(0)R8, OC(0)R8,
OC(0)OR8, NH2, NHR8, NHC(0)R8, NR8C(0)R8, NHS(0)2R8, NR8S(0)2R8, NHC(0)OR8, NR8C(0)OR8, NHC(0)NH2, NHC(0)NHR8, NHC(0)N(R8)2, NR8C(0)NHR8,
NR8C(0)N(R8)2, C(0)NH2, C(0)NHR8, C(0)N(R8)2, C(0)NHOH, C(0)NHOR8,
C(0)NHS02R8, C(0)NR8S02R8, S02NH2, S02NHR8, S02N(R8)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R7 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R11, OR11, SR11, S(0)Rn, S02Rn, NHR11, N(Rn)2, C(0)Rn, C(0)NH2, C(0)NHRn, C(0)N(Rn)2, NHC(0)Rn, NRnC(0)Rn, NHS02Rn, NHC(0)ORn, S02NH2, S02NHRn, S02N(Rn)2, NHC(0)NH2, NHC(0)NHRn, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R8 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2, NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
R10 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R11 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R12 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one or more independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13 is alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14,
C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR13S02R , S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R15 is alkyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl.
In one embodiment of Formula (la), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (la), X1, X2, and X3 are CH. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (la), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (la), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (la), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (la), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (la), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (la), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2,
C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (la), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), R1 is C(0)NH2 In another embodiment of Formula (la), R1 is F. In another embodiment of Formula (la), R1 is CI. In another embodiment of Formula (la), R1 is Br. In another embodiment of Formula (la), R1 is CN. In another embodiment of Formula (la), R^s NH2. In another embodiment of Formula (la), R1 is N02. In another embodiment of Formula (la), R1 is CF3. In another embodiment of Formula (la), R1 is C(0)OH. In another embodiment of Formula (la), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (la), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and RHs NH2. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (la), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 is
CH; and X 2z and X 3J are CR 1 ; R1 is OR3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (la), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In one embodiment of Formula (la),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F,
CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R2 is alkyl, phenyl, heterocyclyl, wherein each R2 alkyl is optionally substituted with one or more independently selected R4, OR4, C(0)R4, CO(0)R4, NHC(0)R4, C(0)NHR4, or F, CI, Br or I; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OCH2CH2CH2CH2CH2CH3, C(0)R5, CO(0)R5, NHR5,
NHC(0)R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, CF3, Br or I;
wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl is optionally substituted with one or more independently selected R5, C(0)R5, NHC(0)R5, C(0)NHR5, F, CI, Br or I; wherein R2 is not 4-methylphenyl;
R3 is alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, OH, F, CI, Br or I;
R4 is alkyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl is optionally substituted with one or more independently selected R7, F, CI, Br or I; wherein each R4 aryl and heterocycyl is optionally substituted with one or more independently selected R8, C(0)R8, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, or cycloalkyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, C(0)NH2, C(0)OH, OH, CN, CF3, F, CI, Br or
R6 is alkyl, or heterocyclyl;
R7 is aryl;
R8 is alkyl, aryl, or heterocyclyl;
R9 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R9 alkyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, and R9, are optionally substituted with one or more independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13 is alkyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3- yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, or cycloalkyl; wherein each R13 alkyl is optionally substituted with one or more independently selected R14, OR14, NH2, N(R14)2, NHC(0)R14, OH, CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3- yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, and cycloalkyl is optionally substituted with one or more independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, CN, CF3, F, CI, Br or I;
R14 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one or more independently selected OCH3, OH, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R is alkyl; with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl.
In another embodiment of Formula (la),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N;
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, CN, NH2, N02, CF3, or C(0)OH;
R2 is alkyl, phenyl, heterocyclyl, wherein each R2 alkyl is optionally substituted with one or more independently selected R4, OR4, C(0)R4, CO(0)R4, NHC(0)R4, C(0)NHR4, or F, CI, Br or I; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OCH2CH2CH2CH2CH2CH3, C(0)R5, CO(0)R5, NHR5,
NHC(0)R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, or CF3; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl is optionally substituted with one or more independently selected R5, C(0)R5, NHC(0)R5, or C(0)NHR5; wherein R2 is not 4-methylphenyl;
R3 is alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH;
R4 is alkyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl is optionally substituted with one or more R7; wherein each R4 aryl and heterocycyl is optionally substituted with one or more independently selected R8, C(0)R8, or CI;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, or cycloalkyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, C(0)NH2, C(0)OH, OH, CN, or CF3;
R6 is alkyl, or heterocyclyl;
R7 is aryl;
R8 is alkyl, aryl, or heterocyclyl;
R9 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R9 alkyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
wherein the cyclic moieties represented by R 3 , R 5 , R 6 , R 7 , R 8 , and R 9 , are optionally substituted with one or more independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, or CI; R is alkyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3- yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, or cycloalkyl; wherein each R13 alkyl is optionally substituted with one or more independently selected R14, OR14, NH2, N(R14)2, NHC(0)R14, OH, or CF3;
wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3- yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, and cycloalkyl is optionally substituted with one or more independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, CN, CF3, F, or CI;
R14 is alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one or more independently selected OCH3, or OH; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R15 is alkyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl.
Still another embodiment pertains to compounds having Formula (la), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 358, 359, 360, 361, 362, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (11a)
In another rmula (Ila)
Figure imgf000151_0001
(Ila);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (la); and R2 is phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein the R2 phenyl, heterocyclyl, cycloalkyl, and cycloalkenyl are optionally substituted as described herein for substituents on R2 in Formula (la).
In one embodiment of formula (Ila),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5,
OCH2CH2CH2CH2CH2CH3, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5,
NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2,
NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2,
S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein R2 is not 4-methylphenyl;
R3 is alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2,
NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10,
SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
R10 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10, are optionally substituted with one or more independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13,
NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13 is alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14,
C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15,
C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R15 is alkyl.
In one embodiment of Formula (Ila), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Ha), X1, X2, and X3 are CH. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (Ila), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Ila), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Ila), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Ila), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Ila), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Ila), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ila), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), R1 is C(0)NH2 In another embodiment of Formula (Ila), R1 is F. In another embodiment of Formula (Ila), R1 is CI. In another embodiment of Formula (Ila), R1 is Br. In another embodiment of Formula (Ila), R1 is CN. In another embodiment of Formula (Ila), RHs NH2. In another embodiment of Formula (Ila), R1 is N02. In another embodiment of Formula (Ila), R1 is CF3. In another embodiment of Formula (Ila), R1 is C(0)OH. In another embodiment of Formula (Ila), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2 In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Ila), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and RHs NH2. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is
CR1; and R1 is C(0)OH. In another embodiment of Formula (Ila), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (Ila), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (Ila), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 607, 608, 613, 614, 615, 617, 618, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 682, 683, 684, 685, 686, 687, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (Ilia)
In ano la (Ilia)
Figure imgf000159_0001
(Ilia);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (la); and Rx is as described herein for substituents at the para position in Formula (la) when R2 is phenyl.
In one embodiment of formula (Ilia),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2,
C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
Rx is R5, OCH2CH2CH2CH2CH2CH3, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5,
OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5,
NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein Rx is not 4- methyl;
R3 is alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2,
NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2,
S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; R6 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
R10 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10, are optionally substituted with one or more independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13,
NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13 is alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14,
C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR13S02R , S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R15 is alkyl.
In one embodiment of Formula (Ilia), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Ilia), X1, X2, and X3 are CH. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (Ilia), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Ilia), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Ilia), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Ilia), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Ilia), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Ilia), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ilia), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2,
C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), R1 is C(0)NH2 In another embodiment of Formula (Ilia), R1 is F. In another embodiment of Formula (Ilia), R1 is CI. In another embodiment of Formula (Ilia), R1 is Br. In another embodiment of Formula (Ilia), R1 is CN. In another embodiment of Formula (Ilia), R^s NH2. In another embodiment of Formula (Ilia), R1 is N02. In another embodiment of Formula (Ilia), R1 is CF3. In another embodiment of Formula (Ilia), R1 is C(0)OH. In another embodiment of Formula (Ilia), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is
CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 and
X 3 are CH; and X 2 is CR 1 ; R1 is OR3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia),
XI and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR^ R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Ilia), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia),
X 2z and X 3J are CH; and X 1 is CR1 ; R1 is OR3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR^ R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Ilia), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and RHs NH2. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (Ilia), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In one embodiment of formula (Ilia), Rx is R5, OCH2CH2CH2CH2CH2CH3, C(0)R5, CO(0)R5, NHR5, NHC(0)R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, or CF3; wherein Rx is not 4-methyl. In another embodiment of formula (Ilia), Rx is R5, NHC(0)R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, or C(0)NHOR5; wherein Rx is not 4-methyl. In another embodiment of formula (Ilia), Rx is R5, and R5 is heterocyclyl, which is optionally substituted as described in embodiments herein.
In another embodiment of Formula (III), Rx is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-l(2H)-onyl, 5-fluorophthalazin-l(2H)- onyl, (Z)-3H-benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2-d][l,2,4]triazin-l(2H)-one, isoindolin-l-onyl, or 1,2,3,6-tetrahydropyridinyl. In another embodiment of Formula (III), Rx is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin- l(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-l(2H)-onyl, 5-fluorophthalazin-l(2H)-onyl, (Z)-3H- benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, isoindolin-l- onyl, or pyrrolo[l,2-d] [l,2,4]triazin-l(2H)-one; which are optionally substituted as defined herein. In another embodiment of Formula (III), Rx is ,2,3,6-tetrahydropyridinyl; which is optionally substituted as defined herein.. Still another embodiment pertains to compounds having Formula (Ilia), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 327, 330, 331, 332, 333, 336, 337, 338, 339, 340, 341, 342, 343, 348, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 543, 544, 545, 546, 547, 548, 549, 553, 554, 555, 556, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 607, 608, 613, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 649, 650, 682, 683, 684, 685, 686, 687, 705, 706, 707, 708, 709, 710, 716, 717, and pharmaceutically acceptable salts thereof.
Still another embodiment pertains to compounds having Formula (Ilia), which include Examples 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 547, 548, 549, 550, 551, 552, and pharmaceutically acceptable salts thereof. Embodiments of Formula (TVa)
In another aspect, the present invention provides compounds of Formula (IV a)
Figure imgf000168_0001
(IVa);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (la).
In one embodiment of formula (IVa),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3 is alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R6, OR6, SR6,
S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2,
NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10,
SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
R10 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10, are optionally substituted with one or more independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13,
NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13 is alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14,
C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15,
C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R15 is alkyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl.
In one embodiment of Formula (IV a), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (IV a), X1, X2, and X3 are CH. In another embodiment of Formula (IV a), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (IV a), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (IVa), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (IVa), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (IVa), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (IVa), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (IVa), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (IVa), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVa), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV a), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IV a), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), R1 is
C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), R1 is C(0)NH2 In another embodiment of Formula (IVa), R1 is F. In another embodiment of Formula (IVa), R1 is CI. In another embodiment of Formula (IVa), R1 is Br. In another embodiment of Formula (IVa), R1 is CN. In another embodiment of Formula (IVa), R^s NH2. In another embodiment of Formula (IVa), R1 is N02. In another embodiment of Formula (IVa), R1 is CF3. In another embodiment of Formula (IVa), R1 is C(0)OH. In another embodiment of Formula (IVa), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IVa), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2,
N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa),
X 2z and X 3J are CH; and X 1 is CR1 ; R1 is OR3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IVa), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are
CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), 1 2 3 1 1 3 3
X1 is CH; and Xz and XJ are CR ; R is OR ; wherein R is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (IVa), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (IVa), which include Examples 291 , 292, 293, 294, 295, 296, 297, 298, 299, 300, 301 , 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 563, 564, 577, 579, 580, 581, 582, 583, 584, 596, 607, 649, 650, 682, 683, 684, 685, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (Va)
In another aspect, the present invention provides compounds of Formula (Va)
Figure imgf000175_0001
(Va);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (la).
In one embodiment of formula (Va),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3 is alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2,
NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2,
S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
R10 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10, are optionally substituted with one or more independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13,
NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13 is alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14,
C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R , OR , SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15,
C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R15 is alkyl.
In one embodiment of Formula (Va), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Va), X1, X2, and X3 are CH. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (Va), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Va), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Va), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Va), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Va), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Va), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Va), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), R1 is C(0)NH2 In another embodiment of Formula (Va), R1 is F. In another embodiment of Formula (Va), R1 is CI. In another embodiment of Formula (Va), R1 is Br. In another embodiment of Formula (Va), R1 is CN. In another embodiment of Formula (Va), RHs NH2. In another embodiment of Formula (Va), R1 is N02. In another embodiment of Formula (Va), R1 is CF3. In another embodiment of Formula (Va), R1 is C(0)OH. In another embodiment of Formula (Va), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2 In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Va), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Va), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 is
CH; and X 2z and X 3J are CR 1 ; R1 is OR3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and RHs NH2. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (Va), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (Va), which include
Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 373, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 424, 425, 426, 427, 430, 431, 434, 435, 436, 437, 438, 439, 440, 441, 442, 445, 446, 447, 448, 449, 450, 496, 497, 553, 554, 555, 556, 559, 560, 561, 562, 565, 567, 568, 569, 570, 571, 572, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 597, 598, 599, 600, 601, 602, 603, 604, 608, 613, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 686, 687, 716, 717, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (Via)
(Via);
or pharmaceutically acceptable salts thereof; wherein R1 and R5 are as described herein for Formula (la); and n is 0 or 1.
In one embodiment of formula (Via),
n is 0 or 1 ;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3 is alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2,
NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2,
S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, OH, aryl, or heterocyclyl;
R10 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10, are optionally substituted with one or more independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13,
NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13 is alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14,
C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolyl, thienyl, furanyl, cycloalkyl, and cycloalkenyl is optionally substituted with one or more independently selected R , OR , SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15,
C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14 is alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one or more independently selected OCH3, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, or cycloalkenyl is optionally substituted with one or more independently selected alkyl, or OCH3; and
R15 is alkyl.
In another embodiment of Formula (Via), n is 0. In another embodiment of Formula (Via), n is 1. In another embodiment of Formula (Via), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Via), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Via), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Via), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Via), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Via), R1 is
C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Via), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Via), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Via), R1 is C(0)NH2. In another embodiment of Formula (Via), R1 is F. In another embodiment of Formula (Via), R1 is CI. In another embodiment of Formula (Via), R1 is Br. In another embodiment of Formula (Via), R1 is CN. In another embodiment of Formula (Via), R^s NH2. In another embodiment of Formula (Via), R1 is N02. In another embodiment of Formula (Via), R1 is CF3. In another embodiment of Formula (Via), R1 is C(0)OH. In another embodiment of Formula (Via), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (Via), which include Examples 285, 286, 287, 288, 289, 290, 426, 427, 437, 445, 553, 554, 555, 556, 599, 627, 628, 629, 630, 631, 632, 633, 634, 635, 686, 687, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (lb)
One embodiment of this invention, therefore, pertains to compounds or pharmaceutically acceptable salts, which are useful as inhibitors of NAMPT, the compounds having Formula (lb)
Figure imgf000185_0001
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein each R2 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4,
OC(0)OR4, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH, C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5,
NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH,
C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R4, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R7, OR7, SR7, S(0)R7, S02R7, C(0)R7, OC(0)R7, OC(0)OR7, NH2, NHR7, NHC(0)R7, NR7C(0)R7, NHS(0)2R7,
NR7S(0)2R7, NHC(0)OR7, NR7C(0)OR7, NHC(0)NH2, NHC(0)NHR7, NHC(0)N(R7)2, NR7C(0)NHR7, NR7C(0)N(R7)2, C(0)NH2, C(0)NHR7, C(0)N(R7)2, C(0)NHOH,
C(0)NHOR7, C(0)NHS02R7, C(0)NR7S02R7, S02NH2, S02NHR7, S02N(R7)2, C(0)H, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R4 aryl and heterocycyl is optionally substituted with one, two, three or four independently selected R8, OR8, SR8, S(0)R8, S02R8, C(0)R8, CO(0)R8, OC(0)R8, OC(0)OR8, NH2, NHR8, NHC(0)R8, NR8C(0)R8, NHS(0)2R8, NR8S(0)2R8, NHC(0)OR8, NR8C(0)OR8, NHC(0)NH2,
NHC(0)NHR8, NHC(0)N(R8)2, NR8C(0)NHR8, NR8C(0)N(R8)2, C(0)NH2, C(0)NHR8, C(0)N(R8)2, C(0)NHOH, C(0)NHOR8, C(0)NHS02R8, C(0)NR8S02R8, S02NH2,
S02NHR8, S02N(R8)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2,
S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R7, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R11, OR11, SR11, S(0)Rn, S02Rn, NHR11, N(Rn)2, C(0)Rn, C(0)NH2, C(0)NHRn, C(0)N(Rn)2,
NHC(0)Rn, NRnC(0)Rn, NHS02Rn, NHC(0)ORn, S02NH2, S02NHRn, S02N(Rn)2,
NHC(0)NH2, NHC(0)NHRn, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2,
NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I; R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R11, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R12, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14,
NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14,
S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R13, CO(0)R , OC(0)R , OC(0)OR , NH2, NHR , N(R13)2, NHC(0)R ,
NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3,
OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In one embodiment of Formula (lb), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is
CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (lb), X1, X2, and X3 are CH. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (lb), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (lb), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (lb), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (lb), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (lb), X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (lb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), R1 is C(0)NH2 In another embodiment of Formula (lb), R1 is F. In another embodiment of Formula (lb), R1 is CI. In another embodiment of Formula (lb), R1 is Br. In another embodiment of Formula (lb), R1 is CN. In another embodiment of Formula (lb), RHs NH2. In another embodiment of Formula (lb), R1 is N02. In another embodiment of Formula (lb), R1 is CF3. In another embodiment of Formula (lb), R1 is C(0)OH. In another embodiment of Formula (lb), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb),
X 11 and X3J are CH; and X 2 is CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and RHs NH2. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (lb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (lb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb),
X 11 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and RHs NH2. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is
C(0)OH. In another embodiment of Formula (lb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In one embodiment of Formula (lb), R2 is phenyl which is substituted at the para position with R5; and R5 is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-l(2H)-onyl, 5-fluorophthalazin-l(2H)-onyl, (Z)-3H- benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2- d][l,2,4]triazin-l(2H)-one, or isoindolin-l-onyl.
In one embodiment of Formula (lb),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R2 is alkyl, phenyl, heterocyclyl; wherein each R2 alkyl is optionally substituted with one, two, three or four independently selected R4, OR4, C(0)R4, CO(0)R4NHC(0)R4, NR4C(0)R4, C(0)NHR4, or C(0)N(R4)2; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, S02R5, C(0)R5, CO(0)R5, NHR5, NHC(0)R5, NHS(0)2R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, S02NHR5, CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl is optionally substituted with one, two, three or four independently selected R5, OR5, C(0)R5, N(R5)2, NHC(0)R5, C(0)NHR5, F, CI, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one, two, three or four independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, OH, F, CI, Br or I;
R4, at each occurrence, is independently selected alkyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four independently selected R7, F, CI, Br or I; wherein each R4 aryl cycloalkyl, and heterocycyl is optionally substituted with one, two, three or four independently selected R8, C(0)R8, CO(0)R8, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, NR9C(0)OR9, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)OH, OH, CN, CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl or heterocyclyl; wherein each R6 alkyl is optionally substituted with one, two, three or four independently selected F, CI, Br or I;
R7, at each occurrence, is independently selected aryl, or heterocyclyl;
R8, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R8 alkyl is optionally substituted with one, two, three or four independently selected R12, OR12OH, CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R12, at each occurrence, is independently selected alkyl, heterocyclyl, or cycloalkyl; wherein each R12 alkyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkynyl, aryl,
tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, or cycloalkyl; wherein each R13 alkyl and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NHC(0)OR14, OH, CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, CN, CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, OH, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I; R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with
OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In another embodiment of Formula (lb),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R2 is alkyl, phenyl, heterocyclyl; wherein each R2 alkyl is optionally substituted with one, two, three or four independently selected R4, OR4, C(0)R4, CO(0)R4NHC(0)R4, NR4C(0)R4, C(0)NHR4, or C(0)N(R4)2; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, S02R5, C(0)R5, CO(0)R5, NHR5, NHC(0)R5, NHS(0)2R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5,
S02NHR5, or CF3; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl is optionally substituted with one, two, three or four independently selected R5, OR5, C(0)R5, N(R5)2, NHC(0)R5, or C(0)NHR5;
R3, at each occurrence, is independently selected alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one, two, three or four independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH;
R4, at each occurrence, is independently selected alkyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four independently selected R7; wherein each R4 aryl cycloalkyl, and heterocycyl is optionally substituted with one, two, three or four independently selected R8, C(0)R8, CO(0)R8, F, CI, or Br; R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, NR9C(0)OR9, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)OH, OH, CN, CF3, or F;
R6, at each occurrence, is independently selected alkyl or heterocyclyl;
R7, at each occurrence, is independently selected aryl, or heterocyclyl;
R8, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R8 alkyl is optionally substituted with one, two, three or four independently selected R12, OR12OH, or CF3;
R9, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R12, at each occurrence, is independently selected alkyl, heterocyclyl, or cycloalkyl; wherein each R12 alkyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, or CI;
R13, at each occurrence, is independently selected alkyl, alkynyl, aryl,
tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, or cycloalkyl; wherein each R13 alkyl and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NHC(0)OR14, OH, or CF3; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, CN, CF3, F, or CI;
R14, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, or OH; wherein each R14 aryl, heterocyclyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R , OR16, OH, or CI;
R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
Still another embodiment pertains to compounds having Formula (lb), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 358, 359, 360, 361, 362, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491 492, 493 494. 495 496 497 498 499 500 501 502 503 504 505,
506, 507, 508, 509, 510 511, 512. 513 514 515 516 517 518 519 520 521 522 523 524,
525, 526, 527, 528, 529 530, 531 532. 533 534 535 536 537 538 539 540 541 542 543,
544, 545, 546, 547, 548 549, 550 551 552 553 554 555 556 557 558 559 560 561 562,
563, 564, 565, 566, 567 568, 569. 570. 571 572 573 574 575 576 577 578 579 580. 581,
582, 583, 584, 585, 586 587, 588 589. 590 591 592 593 594 595 596 597 598 599 600,
601, 602, 603, 604, 605 606, 607 608 613 614 615 616 617 618 619 620. 621 622 623,
624, 625, 626, 627, 628 629, 630. 631 632 633 634 635 636 637 638 639 640 641 642,
643, 644, 645, 646, 647 648, 649. 650. 651 652 653 654 655 656 657 658 659 660. 661,
662, 663, 664, 665, 666 667, 668 669. 670 671 672 673 674 675 676 677 678 679 680,
681, 682, 683, 684, 685 686, 687 689 690, 691 692 693 694 695 696 697 698 699,
700, 701, 702, 703, 704 705, 706. 707 708 709 710. 711 712 713 714 715 716 717 718,
719, 720, 721, 722, 723 724, 725 726. 727 728 729 730. 731 732 733 734 735 736 737,
738, 739, 740, 741, 742 743, 744. 745 746 747 748 749 750 751 752 753 754 755 756,
757, 758, 759, 760, 761 762, 763 764. 765 766 767 768 769 770 771 772 773 774 775,
776, 777, 778, 779, 780 781, 782. 783 784 785 786 787 788 789 790 791 792 793 794,
796, 797, 798, 799, 800 801, 802. 803 805 806 807 808 809 810 811 812 813 814 815,
816, 817, 818, 819, 820 821, 822. 823 824 825 826 827 828 829 830 831 832 833 834,
835, 836, 837, 838, 839 840, 841 842. 843 844 845 846 847 848 849 850 851 852 853,
854, 855, 856, 857, 858 859, 860. 861 862 863 864 865 867 869 870 871 872,
873, 874, 875, 876, 877 878, 879. 880. 881 882 883 884 885 886 887 889 890. 891,
892, 893, 894, 895, 896 897, 898 899. 900 901 902 903 904 905 906 907 908 909 910,
911, 912, 913, 914, 915 916, 917 918 919 920. 921 922 923 924 925 926 927 928 929,
930, 931, 932, 933, 934 935, 936. 937 938 939 940. 941 942 943 944 945 946 947 948,
949, 950, 951, 952, 953 954, 955 956. 957 958 959 960. 961 962 963 964 965 966 967,
968, 969, 970, 971, 972 973, 974. 975 976 977 978 979 980 981 982 983 984 985 986,
987, 988, 989, 990, 991 992, 993 994. 995 996 997 998 999 1000 1001 1002, 1003,
1004, 1005, 1006, 1007 1008, 1009, 1010, 1011 1012, 1013, 1014, 1015 1016, 1017, 1018, 1019, 1021, 1022, 1023 1024, 1025, 1026, 1027 1028, 1029, 1030, 1031 1032, 1033, 1034, 1035, 1036, 1037, 1038 1039, 1040, 1041, 1042 1043, 1044, 1045, 1046 1047, 1048, 1049, 1050, 1051, 1052, 1053 1054, 1055, 1056, 1057 1058, 1059, 1060, 1061 1062, 1063, 1064, 1065, 1066, 1067, 1068 1069, 1070, 1071, 1072 1073, 1074, 1075, 1076 1077, 1078, 1079, 1080, 1081, 1082, 1083 1084, 1085, 1086, 1087 1088, 1089, 1090, 1091 1092, 1093, 1094, 1095, 1096, 1097, 1098 1099, 1100, 1101, 1102 1103, 1104, 1105, 1106 1107, 1108, 1109, 1110, 1111, 1112, 1113 1114, 1115, 1116, 1117 1118, 1119, 1120, 1121 1122, 1123, 1124, 1125, 1126, 1127, 1128 1129, 1130, 1131, 1132 1133, 1134, 1135, 1136 1137, 1138, 1139, 1140, 1141, 1142, 1143 1144, 1145, 1146, 1147 1148, 1149, 1150, 1151 1152, 1153, 1154, 1155, 1156, 1157, 1158, 1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, 1168, 1169, 1170, 1171, 1172, 1173, 1174, 1175, 1176, 1177, 1178, 1179, 1180, 1181, 1182, 1183, 1184, 1185, 1186, 1187, 1188, 1189, 1190, 1191, 1192, 1193, 1194, 1195, 1196, 1197, 1198, 1199, 1200, 1201, 1202, 1203, 1204, 1205, 1206, 1207, 1208, 1209, 1210, 1211, 1212, 1213, 1214, 1215, 1216, 1217, 1218, 1219, 1220, 1221, 1222, 1223, 1224, 1225, 1226, 1227, 1228, 1229, 1230, 1231, 1232, 1233, 1234, 1235, 1236, 1237, 1238, 1239, 1240, 1241, 1242, 1243, 1244, 1245, 1246, 1247, 1248, 1249, 1250, 1251, 1252, 1253, 1254, 1255, 1256, 1257, 1258, 1259, 1260, 1261, 1262, 1263, 1264, 1265, 1266, 1267, 1269, 1270, 1271, 1272, 1273, 1274, 1275, 1276, 1277, 1278, 1279, 1280, 1281, 1282, 1283, 1284, 1285, 1286, 1287, 1288, 1289, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308, 1309, 1310, 1311, 1312, 1313, 1314, 1315, 1316, 1317, 1318, 1319, 1320, 1321, 1322, 1323, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332, 1333, 1334, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343, 1344, 1345, 1346, 1347, 1348, 1349, 1350, 1351, 1352, 1353, 1354, 1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1388, 1389, 1390, 1391, 1392, 1393, 1394, 1395, 1396, 1397, 1398, 1399, 1400, 1401, 1402, 1403, 1404, 1405, 1406, 1407, 1408, 1409, 1410, 1411, 1412, 1413, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, 1423, 1424, 1425, 1426, or pharmaceutically acceptable salts thereof.
Embodiments of Formula (lib)
In another rmula (lib)
Figure imgf000200_0001
(Hb);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (lb); and R2 is phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein the R2 phenyl, heterocyclyl, cycloalkyl, and cycloalkenyl are optionally substituted as described herein for substituents on R2 in Formula (lb).
In one embodiment of formula (lib),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2,
NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2,
NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5,
NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH,
C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH,
C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2,
S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydro furanyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14,
NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15,
NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (lib), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (lib), X1, X2, and X3 are CH. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (lib), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (lib), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (lib), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (lib), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (lib), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (lib), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lib), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), R1 is C(0)NH2 In another embodiment of Formula (lib), R1 is F. In another embodiment of Formula (lib), R1 is CI. In another embodiment of Formula (lib), R1 is Br. In another embodiment of Formula (lib), R1 is CN. In another embodiment of Formula (lib), R^s NH2. In another embodiment of Formula (lib), R1 is N02. In another embodiment of Formula (lib), R1 is CF3. In another embodiment of Formula (lib), R1 is C(0)OH. In another embodiment of Formula (lib), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (lib), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib),
X 2z and X 3J are CH; and X 1 is CR1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (lib), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6,
N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (lib), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (lib), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582 583, 584, 585, 586, 587 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601 602, 603, 604, 607, 608 613, 614, 615, 617, 618, 620, 621, 622, 623, 624, 625, 626, 627, 628 629, 630, 631, 632, 633 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647 648, 649, 650, 651, 652 653, 654, 682, 683, 684, 685, 686, 687, 700, 701, 702, 703, 704, 705 706, 707, 708, 709, 710. 711, 712, 713, 714, 715, 716, 717, 718, 719, 723, 724, 725, 726, 727 728, 729, 730, 731, 732 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746 747, 748, 749, 750, 751 752, 753, 754, 755, 756, 758, 759, 760, 761, 762, 763, 764, 765, 766 767, 768, 769, 770, 771 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785 786, 787, 788, 789, 790. 791, 792, 793, 794, 796, 799, 800, 801, 802, 803, 805, 806, 808, 809 810, 811, 812, 813, 814 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828 829, 830, 831, 832, 833 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847 848, 849, 850, 851, 852 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866 867, 868, 869, 870, 871 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886 887, 888, 889, 890, 891 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905 906, 907, 908, 910, 911 912, 913, 914, 915, 916, 917, 918, 919, 920, 922, 923, 924, 925, 926 927, 928, 929, 930, 931 932, 933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945 946, 947, 948, 949, 950. 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964 965, 966, 967, 968, 969 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983 984, 985, 986, 987, 988 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001 1002. 1003, 1004, 1005 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013, 1014, 1015, 1016. 1017, 1018, 1019, 1021 1022, 1023, 1024, 1025, 1026, 1027, 1028,
1029, 1030, 1031 1032. 1033, 1034, 1035, 1036 1037, 1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046 1047 1048, 1049, 1050, 1051 1052, 1053, 1054, 1055, 1056, 1057, 1058, 1059, 1060, 1061 1062. 1063, 1064, 1065, 1066 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076 1077 1078, 1079, 1080, 1081 1082, 1083, 1084, 1085, 1086, 1087, 1088, 1089, 1090, 1091 1092. 1093, 1094, 1095, 1096 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, 1106 1107 1108, 1109, 1110, 1111 1112, 1113, 1114, 1115, 1116, 1117, 1118, 1119, 1120, 1121 1122. 1123, 1124, 1125, 1126 1127, 1128, 1129, 1130, 1131, 1132, 1133, 1134, 1135, 1136 1137 1138, 1139, 1140, 1141 1142, 1143, 1144, 1145, 1146, 1147, 1148, 1149, 1150, 1151 1152. 1153, 1154, 1155, 1156 1157, 1158, 1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166 1167 1168, 1169, 1170, 1171 1172, 1173, 1174, 1175, 1176, 1177, 1178, 1179, 1180, 1181 1182. 1183, 1184, 1185, 1186 1187, 1188, 1189, 1190, 1191, 1192, 1193, 1194, 1195, 1196 1197 1198, 1199, 1200, 1201 1202, 1203, 1204, 1205, 1206, 1207, 1208, 1209, 1210, 1211 1212. 1213, 1214, 1215, 1216 1217, 1218, 1219, 1220, 1221, 1222, 1223, 1224, 1225, 1226 1227 1228, 1229, 1230, 1231 1232, 1233, 1234, 1235, 1236, 1237, 1238, 1239, 1240, 1241 1242. 1243, 1244, 1245, 1246 1247, 1248, 1249, 1250, 1251, 1252, 1253, 1254, 1255, 1256 1257 1258, 1259, 1260, 1261 1262, 1263, 1264, 1265, 1266, 1267, 1269, 1270, 1271, 1272, 1273, 1274, 1275, 1276, 1277, 1278, 1279, 1280, 1281, 1282, 1283, 1284, 1288, 1289, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308, 1309, 1310, 1311, 1312, 1313, 1314, 1315, 1316, 1317, 1318, 1319, 1320, 1321, 1322, 1323, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332, 1333, 1334, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343, 1344, 1345, 1346, 1347, 1348, 1349, 1363, 1364, 1365, 1366, 1367, 1368, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1388, 1389, 1390, 1391, 1392, 1393, 1394, 1395, 1396, 1397, 1398, 1399, 1400, 1401, 1402, 1403, 1404, 1405, 1406, 1407, 1408, 1409, 1410, 1411, 1412, 1413, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, 1423, 1424, 1425, 1426, or pharmaceutically acceptable salts thereof.
Embodiments of Formula (111b)
In another aspect, the present invention provides compounds of Formula (Mb)
Figure imgf000210_0001
(Illb);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (lb); and Rx is as described herein for substituents at the para position in Formula (lb) when R2 is phenyl.
In one embodiment of formula (Mb),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
Rx is R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5,
NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5,
NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2,
NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14,
NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15,
NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when X1, X2, and X3 are CH; Rx is not methyl;
with the proviso that when X1, X2, and X3 are CH; Rx is not methoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (Mb), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Illb), X1, X2, and X3 are CH. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (Illb), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Illb), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Illb), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Illb), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Illb), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Illb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Illb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), R1 is C(0)NH2 In another embodiment of Formula (Illb), R1 is F. In another embodiment of Formula (Illb), R1 is CI. In another embodiment of Formula (Illb), R1 is Br. In another embodiment of Formula (Illb), R1 is CN. In another embodiment of Formula (Illb), RHs NH2. In another embodiment of Formula (Illb), R1 is N02. In another embodiment of Formula (Illb), R1 is CF3. In another embodiment of Formula (Illb), R1 is C(0)OH. In another embodiment of Formula (Illb), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Mb), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Illb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X2 and X3 are CHj and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X2 and X3 are CHj and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or
OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Illb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR^ R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2 In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Illb), X1 is CH; and X2 and X are CR1; and R1 is C(0)OH. In another embodiment of Formula (Illb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In one embodiment of formula (Illb), Rx is R5, OR5, S02R5, C(0)R5, CO(0)R5, NHR5, NHC(0)R5, NHS(0)2R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, S02NHR5 or CF3. In another embodiment of formula (Illb), Rx is R5, and R5 is heterocyclyl, which is optionally substituted as described in embodiments herein.
In another embodiment of Formula (Illb), Rx is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin- 1 (2H)-onyl, 5,6,7,8-tetrahydrophthalazin- 1 (2H)-onyl, 5-fluorophthalazin- 1(2H)- onyl, (Z)-3H-benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2-d][l,2,4]triazin-l(2H)-one, isoindolin-l-onyl, or 1,2,3,6-tetrahydropyridinyl. In another embodiment of Formula (Illb), Rx is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin- l(2H)-onyl, 5,6,7,8-tetrahydrophthalazin- l(2H)-onyl, 5-fluorophthalazin-l(2H)- onyl, (Z)-3H-benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, isoindolin-l-onyl, or pyrrolo[l,2-d][l,2,4]triazin-l(2H)-one; which are optionally substituted as defined herein. In another embodiment of Formula (Illb), Rx is ,2,3,6-tetrahydropyridinyl; which is optionally substituted as defined herein..
Still another embodiment pertains to compounds having Formula (Illb), which include Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 327, 330, 331, 332, 333, 336, 337, 338, 339, 340, 341, 342, 343, 348, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 543, 544, 545, 546, 547, 548, 549, 553, 554, 555, 556, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 607, 608, 613, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 649, 650, 682, 683, 684, 685, 686, 687, 705, 706, 707, 708, 709, 710, 716, 717, 718, 719, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 759, 760, 761, 762, 763, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 796, 799, 802, 803, 806, 808, 809 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820 821, 822, 823, 824,
825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 840 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859 860, 861, 862, 863, 864, 865, 866, 867 869, 870, 871, 873, 874, 875, 876, 877, 878, 879 880, 881, 882, 883, 884, 885, 886, 887 889, 890, 891, 892, 893, 894, 895, 896, 897, 898 899, 900, 901, 902,
903, 904, 905, 906, 907, 908, 910, 911, 912, 913, 914, 915, 916, 917, 918 919, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 966, 967, 968, 969, 970, 971 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986, 987, 988, 989, 990 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007 1008, 1009, 1010. 1011, 1012, 1013, 1014, 1015 1016, 1017, 1018, 1019, 1021 1022, 1023 1024, 1025, 1026 1027, 1028, 1029, 1030, 1031 1032, 1033, 1034, 1035, 1036 1037, 1038 1039, 1040, 1041 1042, 1043, 1044, 1045, 1046 1047, 1048, 1049, 1050, 1051 1052, 1053 1054, 1055, 1056 1057, 1058, 1059, 1060, 1061 1062, 1063, 1064, 1065, 1066 1067, 1068 1069, 1070, 1071 1072, 1073, 1074, 1075, 1076 1077, 1078, 1079, 1080, 1081 1082, 1083 1084, 1085, 1086 1087, 1088, 1089, 1090, 1091 1092, 1093, 1094, 1095, 1096 1097, 1098 1099, 1100, 1101 1102, 1103, 1104, 1105, 1106 1107, 1108, 1109, 1110, 1111 1112, 1113 1114, 1115, 1116 1117, 1118, 1119, 1120, 1121 1122, 1123, 1124, 1125, 1126 1127, 1128 1129, 1130, 1131 1132, 1133, 1134, 1135, 1136 1137, 1138, 1139, 1140, 1141 1142, 1143 1144, 1145, 1146 1147, 1148, 1149, 1150, 1151 1152, 1153, 1154, 1155, 1156 1157, 1158 1159, 1160, 1161 1162, 1163, 1164, 1165, 1166 1167, 1168, 1169, 1170, 1171 1172, 1173 1174, 1175, 1176 1177, 1178, 1179, 1180, 1181 1182, 1183, 1184, 1185, 1186 1187, 1188 1189, 1190, 1191 1192, 1193, 1194, 1195, 1196 1197, 1198, 1199, 1200, 1201 1202, 1203 1204, 1205, 1206 1207, 1208, 1209, 1210, 1211 1212, 1213, 1214, 1215, 1216 1217, 1218 1219, 1220, 1221 1222, 1223, 1224, 1225, 1226 1227, 1228, 1229, 1230, 1231 1232, 1233 1234, 1235, 1236 1237, 1238, 1239, 1240, 1241 1242, 1243, 1244, 1245, 1246 1247, 1248 1249, 1250, 1251 1252, 1253, 1254, 1255, 1256 1257, 1258, 1259, 1260, 1261 1262, 1263 1264, 1265, 1266 1267, 1269, 1270, 1271, 1272 1273, 1274, 1275, 1276, 1277 1278, 1279 1280, 1281, 1282 1283, 1284, 1288, 1289, 1292 1293, 1294, 1295, 1296, 1297 1298, 1299 1300, 1301, 1302 1303, 1304, 1305, 1306, 1307 1308, 1309, 1310, 1311, 1312 1313, 1314 1315, 1316, 1317 1318, 1319, 1320, 1321, 1322 1323, 1324, 1325, 1326, 1327 1328, 1329 1330, 1331, 1332 1333, 1334, 1335, 1336, 1337 1338, 1339, 1340, 1341, 1342 1343, 1344 1345, 1346, 1347 1348, 1349, 1363, 1364, 1365 1366, 1367, 1368, 1370, 1371 1372, 1373 1374, 1375, 1376 1377, 1378, 1379, 1380, 1381 1382, 1383, 1384, 1385, 1386 1387, 1388 1389, 1390, 1391 1392, 1393, 1394, 1395, 1396 1397, 1398, 1399, 1400, 1401 1402, 1403 1404, 1405, 1406 1407, 1408, 1409, 1410, 1411 1412, 1413, 1414, 1415, 1416 1417, 1418 1419, 1420, 1421 1422, 1423, 1424, 1425, 1426 or pharmaceutically acceptable salts thereof. Still another embodiment pertains to compounds having Formula (Illb), which include 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 547, 548, 549, 550, 551, 552, and pharmaceutically acceptable salts thereof.
Embodiments of Formula (TVb)
In )
Figure imgf000220_0001
(IVb);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (lb).
In one embodiment of formula (IVb),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3 S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02 N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6 OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9,
S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2,
S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydro furanyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R , OR , SR14, S(0)R14, S02R , C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14,
NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14,
S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15,
NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In one embodiment of Formula (IVb), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (IVb), X1, X2, and X3 are CH. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (IVb), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (IVb), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (IVb), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (IVb), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (IVb), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (IVb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2,
C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), R1 is C(0)NH2 In another embodiment of Formula (IVb), R1 is F. In another embodiment of Formula (IVb), R1 is CI. In another embodiment of Formula (IVb), R1 is Br. In another embodiment of Formula (IVb), R1 is CN. In another embodiment of Formula (IVb), R^s NH2. In another embodiment of Formula (IVb), R1 is N02. In another embodiment of Formula (IVb), R1 is CF3. In another embodiment of Formula (IVb), R1 is C(0)OH. In another embodiment of Formula (IVb), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb),
X 11 and X3J are CH; and X 2 is CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and RHs NH2. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IVb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X2 and X3 are CHj and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X2 and X3 are CHj and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R^s NH2. Γη another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IVb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are
CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; and R1 is Br. Γη another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1 and R is CN. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1 and R is NH2. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1 and R is N02. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1 and R is CF3. In another embodiment of Formula (IVb), X1 is CH; and X2 and X3 are CR1; and R is C(0)OH. In another embodiment of Formula (IVb), X1 is CH; and
2 3 1 1 3 3
Xz and XJ are CR ; and R is C(0)R ; wherein R is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (IVb), which include Examples 291 , 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 563, 564, 577, 579, 580, 581, 582, 583, 584, 596, 607, 649, 650, 682, 683, 684, 685, 789, 791, 792, 793, 794, 796, 874, 878, 879, 919, 932, 934, 935, 1363, 1364, 1365, 1366, 1367, 1368, 1370, 1371, 1372, or pharmaceutically acceptable salts thereof.
Embodiments of Formula (Vb)
In another aspect, the present invention provides compounds of Formula (Vb)
Figure imgf000227_0001
(Vb);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (lb).
In one embodiment of formula (Vb),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R , S02R , C(0)R , CO(0)R , OC(0)R , OC(0)OR , NH2, NHR , N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14,
NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15,
NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I; R , at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In one embodiment of Formula (Vb), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Vb), X1, X2, and X3 are CH. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (Vb), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Vb), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Vb), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Vb), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Vb), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Vb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2,
C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), R1 is C(0)NH2 In another embodiment of Formula (Vb), R1 is F. In another embodiment of Formula (Vb), R1 is CI. In another embodiment of Formula (Vb), R1 is Br. In another embodiment of Formula (Vb), R1 is CN. In another embodiment of Formula (Vb), R^s NH2. In another embodiment of Formula (Vb), R1 is N02. In another embodiment of Formula (Vb), R1 is CF3. In another embodiment of Formula (Vb), R1 is C(0)OH. In another embodiment of Formula (Vb), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Vb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Vb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1 ; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (Vb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (Vb), which include Examples 1, 2, 3, 4, 5, 8, 9, 10, 13, 14, 16, 17, 18, 20, 21, 23, 24, 25, 26, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 42, 43, 45, 46, 48, 49, 53, 54, 57, 58, 59, 60, 61, 62, 63, 66, 67, 68, 70, 71, 73, 75, 77, 79, 80, 81, 82, 83, 85, 86, 87, 88, 90, 91, 92, 93, 94, 95, 97, 98, 99, 100,
101, 103, 104, 105, 106, 107, 108, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 139, 140, 141, 142, 143, 144, 145, 146, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 159, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 176, 177, 178, 179, 180, 181, 182, 184, 188, 189, 190, 192, 193, 194, 196, 199, 201, 203, 204, 205, 209, 210, 211, 213, 215, 217, 220, 223, 224, 226, 227, 228, 230, 231, 232, 234, 235, 236, 237, 239, 243, 245, 252, 253, 256, 258, 260, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 288, 289, 290, 373, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 424, 426, 427, 430, 431, 435, 436, 437, 440, 441, 442, 445, 446, 447, 449, 450, 496, 497, 553, 554, 555, 556, 559, 560, 562, 567, 568, 569, 570, 571, 572, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 597, 598, 599, 600, 601, 602, 603, 604, 608, 613, 625, 626, 628, 629, 630, 631, 632, 633, 634, 687, 716, 717, 718, 719, 723, 728, 729, 731, 732, 733, 734, 735, 737, 738, 739, 741, 743, 744, 745, 747, 748, 752, 770, 771, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 790, 802, 803, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 826, 827, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 856, 857, 858, 875, 880, 881, 882, 884, 894, 895, 922, 923, 924, 925, 939, 969, 970, 971, 972, 976, 977, 978, 1063, 1064, 1065, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097, 1098, 1100, 1102, 1103, 1104, 1105, 1106, 1108, 1109, 1110, 1111, 1112, 1113, 1114, 1115, 1116, 1117, 1118, 1119, 1120, 1121, 1122, 1123, 1124, 1125, 1127, 1129, 1130, 1132, 1133, 1135, 1136, 1137, 1138, 1139, 1140, 1141, 1142, 1143, 1144, 1145, 1146, 1147, 1148, 1149, 1150, 1152, 1153, 1154, 1155, 1156, 1157, 1158, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, 1168, 1169, 1170, 1171, 1172, 1173, 1174, 1175, 1176, 1177, 1178, 1179, 1180, 1181, 1182, 1183, 1184, 1185, 1186, 1187, 1188, 1189, 1192, 1193, 1194, 1195, 1196, 1197, 1198, 1199, 1201, 1202, 1203, 1204, 1205, 1206, 1207, 1208, 1209, 1210, 1211, 1212, 1213, 1214, 1215, 1216, 1217, 1218, 1219, 1220, 1221, 1222, 1223, 1224, 1225, 1226, 1227, 1228, 1229, 1230, 1231, 1232, 1233, 1234, 1235, 1236, 1239, 1240, 1241, 1242, 1243, 1245, 1260, 1261, 1262, 1263, 1264, 1266, 1267, 1268, 1269, 1270, 1271, 1272, 1273, 1274, 1275, 1276, 1277, 1278, 1310, 1311, 1312, 1313, 1314, 1315, 1316, 1317, 1318, 1319, 1320, 1321, 1322, 1323, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332, 1333, 1334, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343, 1344, 1345, 1346, 1348, 1349, or pharmaceutically acceptable salts thereof.
Embodiments of Formula (VIb)
Figure imgf000235_0001
(VIb);
or pharmaceutically acceptable salts thereof; wherein R1 and R5 are as described herein for Formula (la); and n is 0 or 1.
In one embodiment of formula (VIb),
n is 0 or 1 ;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2; R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I; R , at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14,
NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15,
NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl.
In another embodiment of Formula (Vlb), n is 0. In another embodiment of Formula (VIb), n is 1. In another embodiment of Formula (Vlb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIb), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIb), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIb), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIb), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIb), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIb), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIb), R1 is C(0)NH2 In another embodiment of Formula (VIb), R1 is F. In another embodiment of Formula (VIb), R1 is CI. In another embodiment of Formula (VIb), R1 is Br. In another embodiment of Formula (VIb), R1 is CN. In another embodiment of Formula (VIb), RHs NH2. In another embodiment of Formula (VIb), R1 is N02. In another embodiment of Formula (VIb), R1 is CF3. In another embodiment of Formula (VIb), R1 is C(0)OH. In another embodiment of Formula (VIb), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (VIb), which include Examples 285, 286, 288, 289, 290, 426, 427, 437, 445, 553, 554, 555, 556, 599, 627, 628, 629, 630, 631, 632, 633, 634, 635, 686, 687, 718, 723, 725, 726, 727, 728, 729, 731, 732, 733, 734, 735, 737, 738, 739, 741, 743, 744, 745, 747, 748, 749, 750, 751, 752, 770, 771, 773, 774, 775, 776, 777, 778, 779, 780, 803, 875, 880, 881, 882, 884, 922, 923, 924, 925, 939, 969, 970, 971, 972, 1055, 1056, 1057, 1058, 1059, 1060, 1061, 1062, 1063, 1064, 1065, 1066, 1067, 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076, or pharmaceutically acceptable salts thereof.
Embodiments of Formula (Vllb)
Figure imgf000239_0001
(Vllb);
or pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R13 are as described herein for Formula (lb), and indicates a single or a double bond.
In one embodiment of formula (Vllb),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R6, andR10 are optionally substituted with one, two, three, four, five, or six independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydro furanyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14,
NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2, C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, 1,1- dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR13C(0)R , NHS(0)2R , NR13S(0)2R , NHC(0)OR , NR13C(0)OR , NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (Vllb), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Vllb), X1, X2, and X3 are CH. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (Vllb), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Vllb), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Vllb), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Vllb), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Vllb), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Vllb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vllb), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), R1 is C(0)NH2 In another embodiment of Formula (Vllb), R1 is F. In another embodiment of Formula (Vllb), R1 is CI. In another embodiment of Formula (Vllb), R1 is Br. In another embodiment of Formula (Vllb), R1 is CN. In another embodiment of Formula (Vllb), R^s NH2. In another embodiment of Formula (Vllb), R1 is N02. In another embodiment of Formula (Vllb), R1 is CF3. In another embodiment of Formula (Vllb), R1 is C(0)OH. In another embodiment of Formula (Vllb), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and RHs NH2. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Vllb), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X2 and X3 are CHj and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X2 and X3 are CHj and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Vllb), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and RHs NH2. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (Vllb), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (Vllb), which include Examples 317, 330, 331, 332, 401, 405, 406, 407, 432, 456, 457, 458, 459, 460, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 543, 544, 545, 546, 620, 646, 647, 705, 706, 707, 708, 709, 710, 759, 760, 761, 762, 763, 799, 910, 911, 912, 913, 914, 915, 916, 917, 918, 967, 968, 979, 980, 981, 982, 983, 984, 985, 986, 1014, 1015, 1016, 1017, 1019, 1077, 1078, 1079, 1080, 1254, 1255, 1256, 1257, 1258, 1259, 1279, 1280, 1281, 1282, 1283, 1284, 1384, 1385, or pharmaceutically acceptable salts thereof.
Embodiments of Formula (Ic)
One embodiment of this invention, therefore, pertains to compounds or pharmaceutically acceptable salts, which are useful as inhibitors of NAMPT, the compounds having Formula (Ic)
Figure imgf000246_0001
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2,
NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein each R2 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4,
OC(0)OR4, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH, C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5,
OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5,
NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH,
C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R4, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 7 , OR 7 , SR 7 , S(0)R 7 , S02R 7 , C(0)R7, OC(0)R7, OC(0)OR7, NH2, NHR7, NHC(0)R7, NR7C(0)R7, NHS(0)2R7,
NR7S(0)2R7, NHC(0)OR7, NR7C(0)OR7, NHC(0)NH2, NHC(0)NHR7, NHC(0)N(R7)2, NR7C(0)NHR7, NR7C(0)N(R7)2, C(0)NH2, C(0)NHR7, C(0)N(R7)2, C(0)NHOH,
C(0)NHOR7, C(0)NHS02R7, C(0)NR7S02R7, S02NH2, S02NHR7, S02N(R7)2, C(0)H, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R4 aryl and heterocycyl is optionally substituted with one, two, three or four independently selected R8, OR8, SR8, S(0)R8, S02R8, C(0)R8, CO(0)R8, OC(0)R8, OC(0)OR8, NH2, NHR8, NHC(0)R8, NR8C(0)R8, NHS(0)2R8, NR8S(0)2R8, NHC(0)OR8, NR8C(0)OR8, NHC(0)NH2,
NHC(0)NHR8, NHC(0)N(R8)2, NR8C(0)NHR8, NR8C(0)N(R8)2, C(0)NH2, C(0)NHR8, C(0)N(R8)2, C(0)NHOH, C(0)NHOR8, C(0)NHS02R8, C(0)NR8S02R8, S02NH2, S02NHR8, S02N(R8)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9,
S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2,
S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R7, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R11, OR11, SR11, S(0)Rn, S02Rn, NHR11, N(Rn)2, C(0)Rn, C(0)NH2, C(0)NHRn, C(0)N(Rn)2,
NHC(0)Rn, NRnC(0)Rn, NHS02Rn, NHC(0)ORn, S02NH2, S02NHRn, S02N(Rn)2, NHC(0)NH2, NHC(0)NHRn, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2,
NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R11, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; R , at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I; wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy;
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (Ic), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Ic), X1, X2, and X3 are CH. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1. In another embodiment of
Formula (Ic), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Ic), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Ic), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Ic), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Ic), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Ic), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ic), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), R1 is C(0)NH2 In another embodiment of Formula (Ic), R1 is F. In another embodiment of Formula (Ic), R1 is CI. In another embodiment of Formula (Ic), R1 is Br. In another embodiment of Formula (Ic), R1 is CN. In another embodiment of Formula (Ic), R^s NH2. In another embodiment of Formula (Ic), R1 is N02. In another embodiment of Formula (Ic), R1 is CF3. In another embodiment of Formula (Ic), R1 is C(0)OH. In another embodiment of Formula (Ic), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic),
X 11 and X3J are CH; and X 2 is CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Ic), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is
C(0)OH. In another embodiment of Formula (Ic), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic),
X 11 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is NH2. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (Ic), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In one embodiment of Formula (Ic), R2 is phenyl which is substituted at the para position with R5; and R5 is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-l(2H)-onyl, 5-fluorophthalazin-l(2H)-onyl, (Z)-3H- benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2- d][l,2,4]triazin-l(2H)-one, or isoindolin-l-onyl.
In one embodiment of Formula (Ic), X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R2 is alkyl, phenyl, cycloalkyl, or heterocyclyl; wherein each R2 alkyl is optionally substituted with one, two, three or four independently selected R4, OR4, C(0)R4,
CO(0)R4NHC(0)R4, NR4C(0)R4, C(0)NHR4, or C(0)N(R4)2; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, S02R5, C(0)R5, CO(0)R5, NHR5, NHC(0)R5, NHS(0)2R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, S02NHR5, CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl and cycloalkyl are optionally substituted with one, two, three or four independently selected R5, OR5, C(0)R5, C(0)OR5, N(R5)2, NHC(0)R5, C(0)NHR5, F, CI, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one, two, three or four independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, OH, F, CI, Br or I;
R4, at each occurrence, is independently selected alkyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four independently selected R7, F, CI, Br or I; wherein each R4 aryl cycloalkyl, and heterocycyl is optionally substituted with one, two, three or four independently selected R8, C(0)R8, CO(0)R8, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, NR9C(0)OR9, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)OH, OH, CN, CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl or heterocyclyl; wherein each R6 alkyl is optionally substituted with one, two, three or four independently selected F, CI, Br or I;
R7, at each occurrence, is independently selected aryl, or heterocyclyl; R , at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R8 alkyl is optionally substituted with one, two, three or four independently selected R12, OR12OH, CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R12, at each occurrence, is independently selected alkyl, heterocyclyl, or cycloalkyl; wherein each R12 alkyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, S02R14, NH2, NHR14, N(R14)2, NHC(0)R14, NHC(0)OR14, OH, CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, OH, CN, CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, OH, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In another embodiment of Formula (Ic),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R2 is alkyl, phenyl, cycloalkyl, or heterocyclyl; wherein each R2 alkyl is optionally substituted with one, two, three or four independently selected R4, OR4, C(0)R4,
CO(0)R4NHC(0)R4, NR4C(0)R4, C(0)NHR4, or C(0)N(R4)2; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, S02R5, C(0)R5, CO(0)R5, NHR5, NHC(0)R5, NHS(0)2R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, S02NHR5, or CF3; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl and cycloalkyl are optionally substituted with one, two, three or four independently selected R5, OR5, C(0)R5, C(0)OR5, N(R5)2, NHC(0)R5, or C(0)NHR5;
R3, at each occurrence, is independently selected alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one, two, three or four independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH;
R4, at each occurrence, is independently selected alkyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl is optionally substituted with one, two, three or four independently selected R7; wherein each R4 aryl cycloalkyl, and heterocycyl is optionally substituted with one, two, three or four independently selected R8, C(0)R8, CO(0)R8, F, CI, or Br;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, C(0)R9, NH2, N(R9)2, NHC(0)R9, NR9C(0)OR9, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)OH, OH, CN, CF3, or F;
R6, at each occurrence, is independently selected alkyl or heterocyclyl;
R7, at each occurrence, is independently selected aryl, or heterocyclyl;
R8, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R8 alkyl is optionally substituted with one, two, three or four independently selected R12, OR12OH, or CF3;
R9, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R9 alkyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R12, at each occurrence, is independently selected alkyl, heterocyclyl, or cycloalkyl; wherein each R12 alkyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, or CI;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, S02R14, NH2, NHR14, N(R14)2, NHC(0)R14, NHC(0)OR14, OH, or CF3; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, CN, OH, CF3, F, or CI;
R14, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, or OH; wherein each R14 aryl, heterocyclyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, or CI; R , at each occurrence, is independently selected alkyl; wherein the R alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. Still another embodiment pertains to compounds having Formula (Ic), which include N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(aminomethyl)benzyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(furo[3,2-c]pyridin-4-yl)piperazin- 1 -yfjcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yfjcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(pyridin-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] -5-fluoro- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(thieno[3,2-c]pyridin-4-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(2,3-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4- [(3 -phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N-(4-{ [4-(pyridazin-3-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2,3-dihydro- 1 ,4-benzodioxin-5-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(3-methylbutyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(2-oxopyrrolidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-methyl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(4-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-fluoro-5-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4- { [4-(pyrazin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; 5-methoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [4-(pyrimidin-2 -yl)piperazin- 1 -yl] carbonyl } phenyl) -1,3 -dihydro-2H-isoindole- 2-carboxamide;
5-nitro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; 5-methyl-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-fluorophenyl)piperazin- 1 -yl] carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(2-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4-{ [4-(3-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(4-acetylphenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(2,3-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-{4-[(3-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-chloro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4-phenylpiperazin-l-yl)carbonyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(6-aminohexyl)carbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide;
4- chloro-N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5- methoxy-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 ,3-benzodioxol-5-ylmethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-3-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(pyridazin-3-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(3-fluorophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [(2-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl }phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3-butoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(3,4-dihydroxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-propoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-furylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole -2-carboxamide; N-(4- { [4-(2-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(3-hydroxy-2-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methylbutyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methyl-lH-indazol-5-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5-(trifluoromethyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [2-(2,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-
2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
methyl 5-({4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl} amino)- 1H- indazole-3-carboxylate; N-(4- { [2-(2-oxopyrrolidin- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(5-chloropyridin-2-yl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-indol-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro- 1 ,4-benzodioxin-6-ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(2-fluorobenzoyl)piperazin- 1 -yl]carbonyl} phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(5-methoxy- lH-indol-3-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-propoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-4-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide; N- [4 -( { 2- [4-(dimethylamino)phenyl] ethyl } carbamoyl)phenyl] -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(4-{ [3-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(lR)-3-hydroxy- 1 -phenylpropyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-fluoro-4-methoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2,3-dimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [2-(l,3-benzodioxol-5-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [2-(2-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-isopropoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-methoxypropyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxamide; N- { 4- [(2-phenoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-hydroxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 1 - [(3S)-tetrahydrofuran-3 -yl] - 1 H-pyrazol-4-yl } carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(2-phenylethyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 , 3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(methylthio)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-ethoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole -2-carboxamide; N- { 4- [(2-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 4-[(trifluoromethyl)thio]benzyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-fluorophenyl)pyrrolidin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(lH-imidazol-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(3-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(hydroxymethyl)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(1 -benzodioxol-5-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -isopropyl- lH-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[methyl(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-[4-(thiomorpholin-4-ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(2-furoyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzylpiperidin-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(5-acetamido-2-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(3,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-
2-carboxamide;
N-[4-({ 2-[3-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-( 1 H-imidazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H-isoindole-2- carboxamide; N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1R)- 1 -(3-cyanophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [benzyl(2-hydroxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(4-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(pyridin-2-yl)ethyl]carbamoyl jphenyl)- 1, 3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyanomethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclohexylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[butyl(methyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [4-(dimemylamino)phenyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,4-dihydroisoquinolin-2(lH)-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro-lH-indol-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(phenylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [2-(diemylamino)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-hydroxy-2-phenylethyl)(methyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-aminophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [(2S)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
tert-butyl (1 - { 4-[( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl }piperidin-4- yl)carbamate;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 4- [3-chloro-5 -(trifluoromethyl)pyridin-2-yl]piperazin- 1 -yl } carbonyl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(cyclohexylmethyl)piperazin- 1 -yl]carbonyl} phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(3-chlorobenzyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(diethylcarbamoyl)piperidin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(piperidin-l -yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-hydroxyethyl)piperazin-l -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-hydroxy-6-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(dimethylarnino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-hydroxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5,6-dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(5-fluoropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopropylmethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [(2S)- 1 -methoxypropan-2-yl]carbamoyl }phenyl)-l ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3,4,9-tetrahydro-2H-beta-carbolin-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tert-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({ 4-[4-(trifluoromethyl)phenyl]piperazin- 1 -yl}carbonyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,3-difluoropyrrolidin- 1 -yl)carbonyl]phenyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)- 1 -benzylpyrrolidin-3-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-carbamoylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopropylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(methylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(dimethylamino)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(pentan-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentan-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[( 1 ,3-dioxolan-2-ylmethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(4-fluorophenyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l -phenyl- lH-pyrazol-4-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 2-[4-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methoxyethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(sec-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-{ 4-[bis(2-ethoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [butyl(ethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [isobutyl(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-carbamoylphenyl)-l,3-dihydro-2H-isoindole-2-carboxarnide;
N-(4- { [(2S)-2-(trifluoromethyl)pyrrolidin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-methylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[ethyl(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [(2R)- 1 -hydroxy-3-methylbutan-2-yl]carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,6-dimethylmorpholin-4-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(prop-2-yn- 1 -ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[isopropyl(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[isopropyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-cyanoethyl)(cyclopropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[emyl(isopropyl)carbamoyl]phenyl}-13-dmydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-fluoropyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -N-isopropyl-beta- alanine;
N-{4-[memyl(propyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide; 5,6-dimethoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(4-chlorophenoxy)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethoxy)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-phenyl- 1 ,3-thiazol-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
methyl 2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylate;
2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid;
5-amino-N- [4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; 5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-(aminomethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; 5- [(2-hydroxy-2-methylpropanoyl)amino] -N- [4-(propylcarbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(N,N-dimethylglycyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-[(methylsulfonyl)amino] -N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-[4-(propylcarbamoyl)phenyl]-13-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(4,4,4-trifluorobutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(4-phenylbutanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-methylpentanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(benzyloxy)acetyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(3-phenylpropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [N-(2-furoyl)glycyl] amino jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(2-thienyl)butanoyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-oxo-4-phenylbutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(N-benzoylglycyl)amino]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide;
N-{4-[(4-phenoxybutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(propionylamino)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(hexanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(heptanoylamino)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-[4-(pent-4-enoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(ethoxyacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [(2-methoxyethoxy)acetyl]amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyclopropylacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(4-methylpiperazin-l -yl)propanoyl] amino jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5- carboxylate;
2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-cyclopentylethyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6- dihydropyridine- 1 (2H)-carboxylate;
N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -methyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [( 1 E)-5-phenylpent- 1 -en- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -propyl- lH-pyrazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzyl- lH-pyrazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(2-hydroxyethyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[6-(l -propyl- lH-pyrazol-4-yl)pyridin-3-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[l-(3-methylbutyl)-lH-pyrazol-4-yl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- [4 -(5 -phenylpentyl)phenyl] -1,3 -dihydro-2H-isoindole-2 -carboxamide;
N-[2-fluoro-4-(l -propyl- lH-pyrazol-4-yl)phenyl] -1, 3-dihydro-2H-isoindole -2- carboxamide;
N- { 2-fluoro-4- [ 1 -(3-methylbutyl)- 1 H-pyrazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [ 1 -(isopropylsulfonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(l'-isobutyryl-l',2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(r-benzoyl-1^2^3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-benzoylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxarnide; N- { 4- [4-(isopropylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(phenylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(benzoylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(butyrylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperazine- 1 - carboxylate;
N-[4-(4-propionylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole -2-carboxamide;
N-{ 4-[4-(cyclopropylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide; N-(2-butyryl-23-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-isobutyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-benzoyl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[2-(3-methylbutyl)-2,3-dihydro-lH-isoindol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexyloxy)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[6-(4-chlorophenoxy)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(piperidin-4-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N,N'-hexane-l,6-diylbis(l,3-dihydro-2H-isoindole-2-carboxamide);
N-(4 -phenylbutyl) -1,3 -dihydro -2H-isoindole-2-carboxamide ;
ethyl 6-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]hexanoate;
N-hexyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-octyl-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [( 1 -methyl- 1 H-pyrazol-4-yl)amino] -6-oxohexyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[6-(memylamino)-6-oxohexyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N- { 6-0X0-6- [(3-phenylpropyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(3-methylbutyl)amino] -6-oxohexyl} -l,3-dihydro-2H-isoindole-2-carboxamide;
N-(5 - { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl }pyridin-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 5-[(3-phenylpropyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{5-[(3-methylbutyl)carbamoyl]pyridin-2-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 5-[(3-phenylpropyl)carbamoyl] - 1 ,3-thiazol-2-yl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 5-[(3-methylbutyl)carbamoyl]- 1 ,3-thiazol-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(isoquinolin-4-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4, 5,6,7, 8-hexahydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(8-fluoro-4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
5-fluoro-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -5-(pyrrolidin- 1 -ylmethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-(morpholin-4-ylmethyl)-N-[4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-methoxy-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- [(4-methylpiperazin- 1 -yl)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-
2-carboxamide;
5-chloro-N- [4-( 1 -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-4,5-dihydro-3H-2,3-benzodiazepin-l-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -5 -(pyrrolidin- 1 -ylmethyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(4-methylpiperazin-l-yl)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide; 5-[(diethylamino)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } -5-(pyrrolidin- 1 - ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-[(l -methylpiperidin-4-yl)oxy] -N- [4-(4-oxo-3,4-dihydrophthalazin-l -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-{ [(3R)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-{ [(3S)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(azetidin- 1 -ylmethyl)-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperidine- 1 - carboxylate;
N-[4-(5-propyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(piperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 5-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-butyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[5-(3-methylbutyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-benzyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [(5-chloropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-hydroxy-4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-oxopyrrolidin- 1 -yl)benzyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(lS,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(l-hydroxycyclopropyl)methyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4-{6-[(1 -dmydro-2H-isoindol-2-ylcarbonyl)amino]-lH-benzimidazol-2- yl}piperazine-l-carboxylate;
N-[2-(piperazin- 1 -yl)- lH-benzimidazol-6-yl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] -5-vinyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-benzoylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[5-(tetrahydrofuran-3-yl)-l,2,4-oxadiazol-3-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- d]pyrimidine-6-carboxamide;
N-(4-{ [(3-phenylpropyl)amino]carbonyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- d]pyrimidine-6-carboxamide; N-{4-[l-(4-memylbenzoyl)-l,2 ,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -benzyl- 1,2,3, 6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(tetrahydrofuran-3-ylmethyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2S)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2R)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [( 1 S) -2-hydroxy- 1 -phenylethyl] amino } carbonyl)phenyl] -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [4-(2-methoxyethyl)piperazin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-2-(2-hydroxyethyl)piperidin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-3-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-4-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N5-(2-methoxyethyl)-N2-{4-[(propylamino)carbonyl]phenyl}-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N-(4-cyanophenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(trifluoromethyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4 - { [(tetrahydrofuran-3 -ylmethyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-pyridin-2-ylpiperazin-l-yl)carbonyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
5-(l ,2-dihydroxyethyl)-N- { 4-[(propylamino)carbonyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l-benzoylpiperidin-4-yl)butyl]-5-cyano-l,3-dihydro-2H-isoindole-2- carboxamide;
N l'-butyryl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(r-isobutyryl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide; and
N-[2-(4-acetylpiperazin-l-yl)-lH-benzimidazol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(5-oxo-D-prolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -propionyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [ 1 -(2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(ethoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[l-(3-memylbenzoyl)-l,2 ,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(2-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(3-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(4-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(4-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(4-chlorobenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[3-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[4-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(3-furoyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[l -(3-thienylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(lH-pyrrol-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2,5 -dimethyl- lH-pyrrol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,3-thiazol-4-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(lH-pyrazol-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(3,5 -dimethyl- 1 ,2-oxazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-
2H-isoindole-2-carboxamide; N-{4-[l-(pyridin-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-( 1 -isonicotinoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(pyridazin-3-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrimidin-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[3-(piperidin- 1 -yl)propanoyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ l-[(4-methylpiperazin-l-yl)acetyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(r-benzoyl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [6-(benzoylamino)hexyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[(benzoylamino)methyl]benzyljcarbamoyl)phenyl]-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [4-(5-oxo-L-prolyl)piperazin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(5-oxo-D-prolyl)piperazin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[(l -acetylpiperidin-4-yl)carbonyl]piperazin-l -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(2-acetamidobenzoyl)piperazin-l -yljphenyl} -l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[4-(methylsulfonyl)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-butyrylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(4-isobutyrylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[4-(2-methylbutanoyl)piperazin- 1 -yljphenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{ 4-[4-(3,3 -trifluoropropanoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(methoxyacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[4-(tetrahydrofuran-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(cyclopentylacetyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(cyclohexylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(2-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(2-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(3-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[3-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {4-[4-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(3,4-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(3,5-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4 - { 4 - [(3 ,4 -dimethoxyphenyl) acetyl] piperazin- 1 -yl } phenyl)- 1 , 3 -dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(2-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [4-(3-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[4-(lH-pyrrol-2-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(lH-pyrazol-5-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [4-(pyridin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(pyridin-3-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-isonicotinoylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyridazin-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrazin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrimidin-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(N,N-dimethyl-beta-alanyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-acetylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole -2-carboxamide; N-{ 4-[4-(2-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(phenylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(l,3-thiazol-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-{4-[4-(morpholin-4-ylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-phenylbutyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -oxo-2, 3-dihydro-lH-isoindol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)cyclohex-3 -en- 1 -yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[l -(3-methylbutyl)- lH-pyrazol-4-yl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[l -(2-phenylethyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N5- [2-(dimethylamino)ethyl] -N2- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {benzyl[3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(isobutoxycarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-bromo-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; 5-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
methyl 4-{ [(5-cyano-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoate; N-(4- { (E)-[(benzyloxy)imino]methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-hydroxy-4-methylpentan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-aminopyrrolidin-l-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-{6-[(3-methylbutyl)carbamoyl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(3-phenylpropyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2,5- dicarboxamide;
N-[4-({benzyl[3-(morpholin-4-yl)propyl] amino }methyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(pyridin-3-yl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -methyl- lH-pyrazol-4-yl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-methoxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide; N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-hydroxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(aminomethyl)-N- { 4-[(cyclopentylacetyl)amino]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-(methylthio)butan-2-yl]carbamoyl}phenyl)-l,3-dihydro-
2H-isoindole-2-carboxamide;
N-(4-{ [(2S,3S)-l-hydroxy-3-methylpentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S,3R)-l,3-dihydroxybutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xyhexan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-1 -hydro xypentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S,2S)-2-hydroxycyclopentyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { [( 1 S ,2R) -2-hydroxycyclopentyl] carb amoyl } phenyl) -1,3 -dihydro -2H-isoindole- 2-carboxamide;
N-(4- { [(2S)- 1 -cyclohexyl-3-hydroxypropan-2-yl] carbamoyl jphenyl)- 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ (2R)- 1 -hydroxy-3-[(4-methylbenzyl)thio]propan-2-yl }carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(IS)- 1 -(4-tert-butylphenyl)-2-hydroxyethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methoxy- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-memyl-N-[4-(propylcarbamoyl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxamide; N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-(4-{ [(2S)-l -hydro xy-4-memylpentan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[6-(benzoylamino)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(pyridin-3 -ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-(pyridin-4-yl)- 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(3-methylbutyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4-phenylbutyl)-1 -dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-[l -(3-methylbutyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 5-[(3-methylbutyl)carbamoyl]pyrazin-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6-acetamidohexyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { ( 1 E) -3 - [benzyl(methyl) amino]prop- 1 -en- 1 -yl } phenyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(4-phenoxypiperidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-phenoxyazetidin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [benzyl(methyl)amino] methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1H- 1 ,2,3-triazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[2-(2-oxopyrrolidin-l-yl)ethyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(l-benzylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-phenylpropyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ l-[4-(morpholin-4-yl)benzyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l-isobutyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(cyclopentylmethyl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methoxypropyl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { 1 -[(2-memoxyemoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{5-[l-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]pyridin-2-yl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-3-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4- { [(2 -methoxyethoxy) acetyl] amino jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(l'-isobutyryl-l',2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(l'-benzoyl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [4-(methylsulfonyl)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6 -[(ethoxyacetyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{6 -[(cyclopentylcarbonyl)amino]hexyl}-1 -dmydro-2H-isoindole-2-carboxamide;
N-{6 -[(2-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{6 -[(3-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{6 -[(4-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{6 - [(2-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N-{6 -[(3-methoxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{6 - [(4-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N-{6 -[(2-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{6 -[(3-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{6 -[(4-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 6- [(2-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(3-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(3-cyanobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-cyanobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(6-{ [3-(dimemylamino)benzoyl]amino jhexyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [4-(dimemylamino)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6-{ [3-(trifluoromethyl)benzoyl]amino jhexyl)- l,3-dihydro-2H-isoindole -2- carboxamide;
N-(6- { [4-(trifluoromethyl)benzoyl]amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [3-(trifluoromethoxy)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,3-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,4-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,5-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(phenylacetyl)amino]hexylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-(6- { [(3-fluorophenyl)acetyl]amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-2-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(ethoxyacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H-isoindole-2 carboxamide;
5-(hydroxymethyl)-N-{4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]phenylj-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-{4-[(morpholin-4-ylacetyl)amino]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[6-(benzoylamino)hexyl]-13-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; 4- fluoro-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
5- fluoro-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [(pyridin-3 -ylcarbonyl)amino]hexyl } -5-(trifluoromethyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
4- cyano-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5- methyl-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4- chloro-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5- chloro-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(pyridin-2-ylcarbonyl)amino]hexyl}-1 -dihydro-2H-isoindole-2-carboxamide; N- { 4- [ 1 -(pyridin-2-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-2,4'- bipyridin-5-yl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[l'-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ r-[(l-methylpyrrolidin-3-yl)carbonyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}- l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ r-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-r,2',3',6'-tetrahydro-2,4'- bipyridin-5 -yl } - 1 , 3 -dihydro-2H-isoindole-2 -carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(7 -oxo-7- { [(3R)-tetrahydrofuran-3-ylmemyl]aminojheptyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 7-oxo-7-[(tetrahydro-2H-pyran-4-ylmethyl)amino]heptyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(azetidin- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(morpholin-4-ylmethyl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{5-[(4-methylpiperazin-l-yl)methyl]-l,2,4-oxadiazol-3-yl Jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(5- { [(3-methylbutyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{5-[(4-hydroxypiperidin-l-yl)methyl]-l,2,4-oxadiazol-3-yl Jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-chlorobenzoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ 1-[(1 -methylpyrrolidin-3-yl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide; Ν-(4-{ 1-[(1 ,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { Γ- [( 1 -methylpyrrolidin-3-yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3 ,4'-bipyridin-6-yl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3,4'- bipyridin-6-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [3-(dimethylamino)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [4-(2-aminoethyl)- lH-imidazol- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-methoxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ [(4S)-2,2-dimethyl- 1 ,3-dioxolan-4-yl]methyl }carbamoyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ [(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methyljcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino } -2-oxoethyl)phenyl] - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N-[4-(3- {benzyl[3-(morpholin-4-yl)propyl] amino } -3-oxopropyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2R)-butan-2-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methyl- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(6-bromo-2-oxoquinolin-l(2H)-yl)butyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[6-(3-acetylphenyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3-dihydro-2H-isoindole- 2-carboxamide; N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(morpholin-4-ylacetyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[l'-(morpholin-4-ylacetyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(2- { (4-fluorobenzyl)[4-(pyridin-3-yl)benzyl]amino } - 1 ,3-thiazol-5-yl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2 -benzyl- 1 ,3-thiazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(7 - { benzyl [3 -(morpholin-4-yl)propyl] amino } -7 -oxoheptyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)sulfamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(cyclopentylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- { 4-[(l ,3-thiazol-5-ylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1R) -3 -hydroxy- 1 -phenylpropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(4-methylphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N- {4-[(l, 3-dihydroxypropan-2-yl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3 -dihydro -2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-1 -hydroxy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; 5-cyano-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(4-hydroxybutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(3-furylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- {4-[(tetrahydro furan-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(2-furoyl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yljcarbonyl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-tetrahydrofuran-2-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(ethylsulfonyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- {4-[(tetrahydro furan-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(lR)-2-hydroxy- 1 -phenylethyljcarbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2S)-1 -hydro xybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2,3-dihydroxypropyl)carbamoyl]phenylj - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(pyridin-2-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(l -hydroxy-4-methylpentan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide; 5-cyano-N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(5-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}pyridin-2-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.3]hept-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.4]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,9-diazaspiro[5.5]undec-3-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- {benzyl[3-(morpholin-4-yl)propyl] amino } -4-oxobutyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-phenylbutyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino }ethyl)phenyl]- 1 ,3-dihydro-2H- isoindole-2-carboxamide; 5-acetyl-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -hydroxy ethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(butyrylamino)phenyl] -5-cyano- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3-methoxybenzyl)sulfonyl]amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2, 8 -diazaspiro [4.5] dec-2 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2,7 -diazaspiro [4.5] dec-7 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 8 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(2-oxa-7-azaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[6-(3-acetylphenyl)-4-(3-hydroxypropyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { 1 -[(2-memoxyemoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-(acetamidomethyl)-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{5-[2-(2-chlorobenzyl)-l,3-thiazol-4-yl]-2-thienyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-fluorophenyl)butyl]-5-(hydroxymethyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl] methyl } carbamoyl)phenyl] - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydro-2H-pyran-4-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(l-isobutylpiperidin-4-yl)phenyl]-13-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(2-hydroxypropan-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl {4-[(13-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzyl}carbamate; N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(methoxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(5- { [(tetrahydrofuran-2-ylmethyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-(4- {5-[(4-methoxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl Jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(5- { [4-(2-methoxyethyl)piperazin- 1 -yl]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [ 1 -(morpholin-4 -yl)cyclopentyl] methyl } carbamoyl)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-pentanoylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 -acetylpiperidin-4-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butyrylpiperidin-4-yl)oxy]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-4-yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(cyclopropylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[( 1 -acetylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [( 1 -isobutyrylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6-{ [l-(3-methylbutanoyl)piperidin-4-yl]oxyjpyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(methoxyacetyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopropylacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6 - { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl] oxy } pyridin-3 -yl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopentylacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; tert-butyl (2- { 4- [( 1 ,3-dihydro-2H-isoindol-2- ylc arbonyl) amino] phenyl } ethyl)c arb amate ;
N-(4-{ l-[(2R)-tetr ahydrofuran-2-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-cyano-N- { 4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { 1 -[(1 , 1 -dioxidotetrahydromiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(3,3, 3-trifluoropropanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(cyclobutylcarbonyl)azetidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(3 -phenylpropanoyl)pyrrolidin- 3 -yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- [4 -( { 1 - [(4-methoxyphenyl) acetyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)pyrrolidin-3 -yl] oxy } phenyl) -1,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-benzoylpyrrolidin-3-yl)oxy]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4- { [ 1 -(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(l -methylcyclopropyl)carbonyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -acetylpyrrolidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine- 2-carboxamide;
N-(4-{ [l-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethoxyacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ 1-[(1 -methylpiperidin-4-yl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N-{4-[l-(2-methylpropanoyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenylj- 1,3- dihydro-2H-isoindole-2-carboxamide; tert-butyl [( 1 - { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } azetidin-3- yl)methyl]carbamate;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(morpholin-4-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2-methoxyethoxy)acetyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(2,3-dimethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(morpholin-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2,2-dimethylpropanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tricyclo[3.3.1.1~3,7~]dec-l-ylacetyl)azetidin-3-yl]oxy}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [(4-methoxycyclohexyl)carbonyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [4-(acetylamino)phenyl] sulfonyl } amino)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(propylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-propylphenyl)sulfonyl]amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(butylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine-2- carboxamide;
N-{4-[({ [(lS,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-l- yl]methyl } sulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(ethylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(benzylsulfonyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-fluorophenyl)sulfonyl] amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(thiophen-2-ylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,6-diazaspiro[3.5]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(Ν,Ν-dimethylglycyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l-en-l-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] amino } cyclohex- 1 -en- 1 - yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(4,4-difluorocyclohexyl)carbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(piperidin- 1 -ylsulfonyl)phenyl]- 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
5-fluoro-N-(4-{ [l-(l,3-thiazol-2-yl)propan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4,4-difluorocyclohexyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- IH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5-fluoro- l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide; 5-fluoro-N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-D- phenylalaninamide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl}phenyl)-5- fluoro-l,3-dihydro-2H-isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl} -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl} -5 -fluoro- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(5-methyl-lH-pyrazol-l-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-chloro-lH-pyrazol-l-yl)ethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-5,7- dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yljcarbonyl)phenyl]-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-carbamoylbenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 ,7-dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
Nalpha-{4-[(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-ylcarbonyl)amino]benzoyl}-L- phenylalanin amide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl }phenyl)-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5,7-dihydro-6H-pyrrolo [3 ,4- b]pyridine-6-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(4,5,6,7-tetrahydro-lH-indazol-5-ylcarbamoyl)phenyl]-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4- { [(3-methyl- 1 ,2-oxazol-5-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -cyanobutan-2-yl]carbamoyl}phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(lH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[methyl(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrazol-3-yl)methyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- {4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(l -methoxybutan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } -5-fluoro- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl} -5-fluoro- l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(pyridin-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N- { 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropyle thy 1] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(l-methylcyclopropyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4- [(thiophen-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(4-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(2S)- 1 -methoxypropan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrrol-2-yl)methyl] carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyljphenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -amino- 1 -oxobutan-2-yl] carbamoyl }phenyl)-5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(l -methoxypropan-2-yl)carbamoyl]phenylj -l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(cyclopentylcarbamoyl)phenyl]-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-2-methylbutyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5-fluoro-1 -dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l-cyanoethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(5-methyl-l,2-oxazol-3-yl)methyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(3-methyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(1 -methyl- lH-pyrazol-3-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-5 ,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(l,3-thiazol-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -methoxybutan-2-yl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(2-ethoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{ 4-[( 1 -cyanocyclopropyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(5-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(4-methyl-l,3-thiazol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-{4-[(2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(lR)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-{4-[(thiophen-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [(1 S)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(l-memyl-lH-pyrrol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(dimemylarrdno)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-{4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-{ 4-[( 1 -cyanoethyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-{4-[methyl(propyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b] pyridine-6-carboxamide;
methyl 1 - { 4- [( 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } azetidine-3-carboxylate;
N-(4- { 3-[(3-methylbutyl)carbamoyl]azetidin- 1 -yl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydrofuran-2-ylmethyl)carbamoyl] azetidin- 1 -yljphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [3 -(benzylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c] pyridine-2-carboxamide;
N- { 4- [3 -(cyclopentylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 3-[(cyclopentylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{3-[(2-methoxyethyl)carbamoyl]azetidin-l -yljphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(cyclopentylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l-(tetrahydrofuran-2-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-2-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(pyrrolidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4,4-difluorocyclohexyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-memyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyljpyridazin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({2-[(dimethylamino)methyl]benzyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,3-oxazol-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole -2-carboxamide; N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [2-(furan-2-yl)-2-(pyrrolidin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydrofuran-3-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- {4-[l-(tetrahydro-2H-pyran-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl }- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(4-fluorobenzyl)(3-methylbutanoyl)amino]butyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6H-furo[2',3':2,3]cyclobuta[l,2- c]quinolin-6-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[7-chloro-l-(2-hydroxyethyl)-3-oxo-l,3-dihydrocyclobuta[c]quinolin-4(2H)- yl]butyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-acetylpiperidin-3-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N- { 4- [( 1 -butanoylpiperidin-3 -yl)oxy] phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-3 -yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-3-yl]oxyjphenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [3-(3,5 -dimethyl- 1 H-pyrazol- 1 -yl)propyl] carbamoyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide; N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 ,3 -thiazol-2-yl)ethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(2,2-difluoroethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-4-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -L- phenylalaninamide;
N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(thiophen-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(5-methyl- IH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-3-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -methoxybutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pyrimidin-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-( 1 H-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-methylbutyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}butyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(propan-2-yloxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(4,4,4-trifluorobutanoyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(1 -acetylpiperidin-4-yl)carbonyl] amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(ethoxyacetyl)amino]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [(tetrahydrofuran-2-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-{ 4-[(cyclopentylcarbonyl)amino]phenyl } - 1 ,3-dmydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{7-oxo-7-[(3-phenylpropyl)amino]heptyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(bicyclo[2.2 ]hept-2-ylacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 ,3-thiazol-5-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(4-0X0-4, 5,6,7-tetrahydro-l-benzofuran-3-yl)carbonyl] amino jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {2-[(3-methylbutanoyl)amino]ethyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{2-[(4-methylpentanoyl)amino]ethyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(ethoxy acetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(2- { [(2-methoxyethoxy)acetyl] amino } ethyl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-2-ylcarbonyl) amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(cyclopentylcarbonyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(cyclopentylacetyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[2-(benzoylamino)ethyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{2-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]ethyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydro-2H-pyran-4 -ylacetyl)amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-3 -ylacetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole-
2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-{ 4-[( 1 -propanoylazetidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-ethylbutanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(pent-4-ynoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)azetidin-3 -yl]oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethylglycyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethyl-beta-alanyl)azetidin-3 -yljoxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrrolidin- 1 -ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(pyrrolidin-l-yl)propanoyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [3-(piperidin- 1 -yl)propanoyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[(4-methylpiperazin- 1 -yl)acetyl] azetidin- 3 -yl }oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(4-methylpiperazin-l-yl)propanoyl]azetidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopropylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(2-cyclopentylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3,3-dimethylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(tetrahydrofuran-2-ylmethyl)piperidin-4-yl] oxy } phenyl) -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(butylsulfonyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylsulfonyl)piperidin-4-yl] oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(4-fluorophenyl)sulfonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propan-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(benzylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(thiophen-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-({ l-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(4,4-difluorocyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-D-prolyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylpropanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpentanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-ethylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4 - { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)piperidin-4-yl] oxy jphenyl) -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(l,2 -oxazol-5 -ylcarbonyl)piperidin-4-yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridazin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrazin-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(piperidin-l-yl)propanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[3-(4-methylpiperazin- 1 -yl)propanoyl]piperidin-4-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; benzyl trans-3-[(l,3-dmydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl)amino]cyclobutanecarboxylate;
N-[4-(4- { [(4-methylpiperazin- 1 -yl)acetyl] amino jcyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(benzoylamino)cyclohex- 1 -en- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 -methylpiperidin-4-yl)carbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4-{ [(1,1 -dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl] amino } cyclohex- 1 -en-
1 -yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3R)-tetrahydrofuran-3-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3S)-tetrahydrofuran-3 -ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-2-methylbutanoyl]amino jcyclohex- 1 -en-1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 3 - [(3 -methylbu tanoyl) amino] oxetan-3 -yl } phenyl) - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
tert-butyl 4-({4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } sulfonyl)piperidine- 1 -carboxylate;
N-{ 4-[4-(propylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(2-methoxyethyl)carbamoyl]piperidin- 1 -yl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(cyclopentylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(l ,4-dioxan-2-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [4-(cyclopentylcarbamoyl)piperidin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N- { 4- [4-(tetrahydro-2H-pyran-4-ylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(morpholin-4-ylcarbonyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[4-(cyclopropylcarbamoyl)piperidin-l-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-hydroxy-2-methylpropyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(butan-2-ylcarbamoyl)piperidin- 1 -yljphenyl } -1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetrahydrofuran-3-ylcarbonyl] -1,2,3, 6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { (4R)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { (4S)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzoylazetidin-3-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-benzoylazetidin-3-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[trans-3-(benzylcarbamoyl)cyclobutyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{trans-3-[(2-phenylethyl)carbamoyl]cyclobutylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N- { trans-3- [(3-phenylpropyl)carbamoyl] cyclobutyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methyl- 1 ,3-oxazol-4-yl)carbonyl]- 1 ,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(furan-3-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-3-(furan-2-yl)prop-2-enoyl] -1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,3-oxazol-5-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3,3,3-trifluoropropanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,5 -dimethyl- 1 H-pyrazol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methoxycyclohexyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,3-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-difluorocyclopropyl)carbonyl] -1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(lH-pyrazol-5-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tert-butoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-l,2,4-triazol-l-yl)propanoyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-ethoxypropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-hydroxy-3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-pyrrol- l-yl)propanoyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylcyclopropyl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2-methylpropoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l-(l-memylprolyl)-l,2 ,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -hydroxycyclopropyl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l - { [1 -(methoxymethyl)cyclopropyl]carbonyl } - 1 ,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(methylsulfonyl)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -acetyl- 1 ,2, 3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4- [1 -(eye loprop ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-4-methylpent-2-enoyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-methoxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopent- 1 -en- 1 -ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 - dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(thiophen-3-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-propanoyl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [ 1 -(2,2-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrrol-2-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,2-dimethylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(4-methylhexanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-dimethylcyclopropyl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-5-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclobutylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(piperidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[2-(pyrrolidin- 1 -yl)propanoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2-methoxyethoxy)acetyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -(trans-4- { [(2 -methoxyethoxy) acetyl] amino } cyclohexyl)phenyl] -1,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } eye lohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}pyridazin-3-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ [(3R)-l-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl] oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ (3R)- 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3R)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(bicyclo[2.2.1]hept-2-ylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(2-methylpropanoyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(2-methylpropanoyl)amino]cyclohexyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(cyclohexylcarbonyl)amino]cyclohexyljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { trans-4- [(cyclohexylcarbonyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(cyclopropylacetyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {cis-4-[(cyclopropylacetyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(cyclopentylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l -en-1 -yljphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; and pharmaceutically acceptable salts thereof.
Still another embodiment pertains to compounds of Formula (Ic), which are
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamo yljphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonylj- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 -dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide; N-(4 - { 1 - [( 1 , 1 -dioxidotettahydro-2H
tetrahydropyridin-4-yl}phenyl)-13-dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Still another embodiment pertains to compounds of Formula (Ic), which are
N-(4- { [(3S)-tettahydrofuran-3-ylmethyl]carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Embodiments of Formula (lie)
In another rmula (lie)
Figure imgf000341_0001
(lie);
and pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (Ic); and R2 is phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein the R2 phenyl, heterocyclyl, cycloalkyl, and cycloalkenyl are optionally substituted as described herein for substituents on R2 in Formula (Ic).
In one embodiment of formula (lie),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1 ; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2,
NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5,
C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5,
NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH,
C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH,
C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2,
NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with
OR5; R5 is not methyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (lie), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (lie), X1, X2, and X3 are CH. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (lie), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (lie), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (lie), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (lie), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (lie), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (lie), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lie), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6,
N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), R1 is C(0)NH2 In another embodiment of Formula (lie), R1 is F. In another embodiment of Formula (lie), R1 is CI. In another embodiment of Formula (lie), R1 is Br. In another embodiment of Formula (lie), R1 is CN. In another embodiment of Formula (lie), RHs NH2. In another embodiment of Formula (lie), R1 is N02. In another embodiment of Formula (lie), R1 is CF3. In another embodiment of Formula (lie), R1 is C(0)OH. In another embodiment of Formula (lie), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie),
X 11 and X3J are CH; and X 2 is CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is
CR1; and R1 is C(0)OH. In another embodiment of Formula (lie), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (lie), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie),
X 11 is CH; and X 2z and X 3J are CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (lie), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (lie), which include
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(aminomethyl)benzyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(furo[3,2-c]pyridin-4-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(pyridin-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] -5-fluoro- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(thieno[3,2-c]pyridin-4-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(2,3-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4- [(3 -phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [4-(pyridazin-3-yl)piperazin-l -yljcarbonyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2,3-dihydro- 1 ,4-benzodioxin-5-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4-{ [l-(3-methylbutyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [4-(pyridin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-(4-{ [3-(2-oxopyrrolidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-methyl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(4-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-fluoro-5-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [4-(pyrazin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; 5-methoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [4-(pyrimidin-2 -yl)piperazin- 1 -yl] carbonyl } phenyl) -1,3 -dihydro-2H-isoindole- 2-carboxamide;
5-nitro-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-fluorophenyl)piperazin- 1 -yl] carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(2-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(3-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [4-(4-acetylphenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(2,3-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-chloro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4-phenylpiperazin-l-yl)carbonyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(6-aminohexyl)carbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide;
4- chloro-N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5- methoxy-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 ,3-benzodioxol-5-ylmethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-3-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridazin-3-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide; N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(3-fluorophenyl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl }phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3-butoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [2-(3,4-dihydroxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-propoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-furylmethyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide; N-(4- { [4-(2-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(3-hydroxy-2-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methylbutyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methyl-lH-indazol-5-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5-(trifluoromethyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(2,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
methyl 5-({4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl} amino)- 1H- indazole-3-carboxylate;
N-(4- { [2-(2-oxopyrrolidin- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide; N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(5-chloropyridin-2-yl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-indol-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro- 1 ,4-benzodioxin-6-ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(2-fluorobenzoyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(5-methoxy- lH-indol-3-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(2-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-propoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-4-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- [4 -( { 2- [4-(dimethylamino)phenyl] ethyl } carbamoyl)phenyl] -1,3 -dihydro -2H- isoindole-2-carboxamide; N-(4-{ [3-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-13-dmydro-2H-isoindole-2- carboxamide;
N-(4- { [(lR)-3-hydroxy- 1 -phenylpropyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-fluoro-4-methoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(l ,3-benzodioxol-5-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(2-methoxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-isopropoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-methoxypropyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [(2,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxamide; N-{ 4-[(2-phenoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [2-(4-hydroxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 1 - [(3S)-tetrahydrofuran-3 -yl] - 1 H-pyrazol-4-yl } carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(2-phenylethyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(methylthio)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-ethoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole -2-carboxamide; N- { 4- [(2-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 4-[(trifluoromethyl)thio]benzyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-fluorophenyl)pyrrolidin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(lH-irnidazol-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(3-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(hydroxymethyl)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-benzodioxol-5-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [( 1 -isopropyl- lH-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[methyl(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(thiomoφholin-4-ylcarbonyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(2-furoyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzylpiperidin-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(5-acetamido-2-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(3,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ 2-[3-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-( 1 H-imidazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [(1R)- 1 -(3-cyanophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [benzyl(2-hydroxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(4-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(pyridin-2-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyanomethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclohexylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[butyl(methyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [4-(dimemylamino)phenyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,4-dihydroisoquinolin-2(lH)-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro-lH-indol-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(phenylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [2-(diemylamino)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-hydroxy-2-phenylethyl)(methyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-aminophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1, 3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide; tert-butyl (1 - { 4-[( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl }piperidin-4- yl)carbamate;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 4- [3-chloro-5 -(trifluoromethyl)pyridin-2-yl]piperazin- 1 -yl } carbonyl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(cyclohexylmethyl)piperazin- 1 -yl]carbonyl} phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(3-chlorobenzyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(diethylcarbamoyl)piperidin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-hydroxyethyl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-hydroxy-6-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(dimethylarnino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-hydroxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5,6-dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(5-fluoropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopropylmethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(l,3,4,9-tetrahydro-2H-beta-carbolin-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tert-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({ 4-[4-(trifluoromethyl)phenyl]piperazin- 1 -yl}carbonyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,3-difluoropyrrolidin- 1 -yl)carbonyl]phenyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)- 1 -benzylpyrrolidin-3-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-carbamoylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopropylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(methylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(dimethylamino)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(pentan-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentan-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[( 1 ,3-dioxolan-2-ylmethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(4-fluorophenyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[( 1 -hydroxy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; Ν-{4-[(1 -phenyl- lH-pyrazol-4-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 2-[4-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methoxyethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(sec-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[bis(2-ethoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [butyl(ethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [isobutyl(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-carbamoylphenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)-2-(trifluoromethyl)pyrrolidin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [(2-methylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[ethyl(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[(2,6-dimethylmoφholin-4-yl)carbonyl]phenyl}-1 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(prop-2-yn- 1 -ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [isopropyl(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[isopropyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-cyanoethyl)(cyclopropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[emyl(isopropyl)carbamoyl]phenyl}-13-dmydro-2H-isoindole-2-carboxamide; N- { 4- [(3-fluoropyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -N-isopropyl-beta- alanine;
N-{4-[memyl(propyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide; 5,6-dimethoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [3-(4-chlorophenoxy)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethoxy)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-phenyl- 1 ,3-miazol-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
methyl 2- { [4-(propylcarbamoyl)phenyl] carbamoyl } isoindoline-5-carboxylate;
2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid;
5-amino-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-(aminomethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(2-hydroxy-2-methylpropanoyl)amino] -N-[4-(propylcarbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide; 5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(N,N-dimethylglycyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-[(methylsulfonyl)amino] -N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-[4-(propylcarbamoyl)phenyl]-13-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(4,4,4-trifluorobutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(4-phenylbutanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-methylpentanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(benzyloxy)acetyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenylpropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [N-(2-furoyl)glycyl] amino jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(2-thienyl)butanoyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(4-oxo-4-phenylbutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(N-benzoylglycyl)amino]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-{4-[(4-phenoxybutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(propionylamino)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(hexanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(heptanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pent-4-enoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(ethoxyacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2-methoxyethoxy)acetyl]amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyclopropylacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [3-(4-methylpiperazin-l-yl)propanoyl] amino jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5- carboxylate;
2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-cyclopentylethyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6- dihydropyridine- 1 (2H)-carboxylate;
N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -methyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 E)-5-phenylpent- 1 -en- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -propyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(l -benzyl- lH-pyrazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(2-hydroxyethyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-[6-(l -propyl- lH-pyrazol-4-yl)pyridin-3-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[l-(3-methylbutyl)-lH-pyrazol-4-yl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- [4 -(5 -phenylpentyl)phenyl] -1,3 -dihydro-2H-isoindole-2 -carboxamide;
N-[2-fluoro-4-(l -propyl- lH-pyrazol-4-yl)phenyl] -1, 3-dihydro-2H-isoindole -2- carboxamide;
N- { 2-fluoro-4- [ 1 -(3-methylbutyl)- 1 H-pyrazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetr ahydropyridin-4-yl)phenyl]- 1, 3-dihydro-2H-isoindo le-2- carboxamide;
N- { 4- [ 1 -(isopropylsulfonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(r-isobutyryl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(l'-benzoyl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-benzoylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(isopropylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(phenylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(benzoylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(butyrylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperazine- 1 - carboxylate;
N-[4-(4-propionylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[4-(cyclopropylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-butyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-(2-isobutyryl-2 -dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-benzoyl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[2-(3-methylbutyl)-2,3-dihydro-lH-isoindol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexyloxy)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(5 - { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl }pyridin-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{5-[(3-phenylpropyl)carbamoyl]pyridin-2-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{5-[(3-methylbutyl)carbamoyl]pyridin-2-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 5-[(3-phenylpropyl)carbamoyl] - 1 ,3-thiazol-2-yl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 5-[(3-methylbutyl)carbamoyl]- 1 ,3-thiazol-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(isoquinolin-4-yl)phenyl]-1 -dmydro-2H-isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4, 5,6,7, 8-hexahydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(8-fluoro-4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
5-fluoro-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5-(pyrrolidin-l-ylmethyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(morpholin-4-ylmethyl)-N-[4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-methoxy-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- [(4-methylpiperazin- 1 -yl)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide; 5-cyano-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-chloro-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-4,5-dihydro-3H-2,3-benzodiazepin-l-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -5 -(pyrrolidin- 1 -ylmethyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5- [(4-methylpiperazin- 1 -yl)methyl] -N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } -5 -(pyrrolidin- 1 - ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-[(l -methylpiperidin-4-yl)oxy] -N- [4-(4-oxo-3,4-dihydrophthalazin-l -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-{ [(3R)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-{ [(3S)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(azetidin- 1 -ylmethyl)-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
tert-butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperidine- 1 - carboxylate; N-[4-(5-propyl-l,2,4-o adiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(piperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 5-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-butyrylpiperidin-4-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(l -isobutyrylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(l -benzoylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[5-(3-methylbutyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-benzyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3R)-tetrahydrofuran-3-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(5-chloropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-hydroxy-4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-oxopyrrolidin- 1 -yl)benzyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [(lS,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(l-hydroxycyclopropyl)methyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide; tert-butyl 4-{6-[(1 -dmydro-2H-isoindol-2-ylcarbonyl)amino]-lH-benzimidazol-2- yl } piperazine- 1 -carboxylate;
N-[2-(piperazin- 1 -yl)- lH-benzimidazol-6-yl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-vinyl-13-dmydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-benzoylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(tetrahydrofuran-3-yl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- d]pyrimidine-6-carboxamide;
N-(4-{ [(3-phenylpropyl)amino]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- d]pyrimidine-6-carboxamide;
N-{4-[l-(4-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -benzyl- 1,2,3, 6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(tetrahydrofuran-3-ylmethyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2S)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2R)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [(1 S)-2-hydroxy- 1 -phenylethyl] amino }carbonyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [4-(2-methoxyethyl)piperazin-l -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-2-(2-hydroxyethyl)piperidin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-3-yl-l,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-4-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N5-(2-methoxyethyl)-N2-{4-[(propylamino)carbonyl]phenyl}-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N-(4-cyanophenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(trifluoromethyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4 - { [(tetrahydrofuran-3 -ylmethyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-pyridin-2-ylpiperazin-l-yl)carbonyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro-
2H-isoindole-2-carboxamide;
5-( 1 ,2-dihydroxyethyl)-N- { 4- [(propylamino)carbonyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(l'-butyryl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(r-isobutyryl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide; and
N-[2-(4-acetylpiperazin-l-yl)-lH-benzimidazol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(5-oxo-D-prolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -propionyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [ 1 -(2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(ethoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(2-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(3-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(4-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(4-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(4-chlorobenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[3-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[4-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide; N-{ 4-[l -(3-furoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[l -(3-thienylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(lH-pyrrol-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2,5 -dimethyl- lH-pyrrol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,3-thiazol-4-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(lH-pyrazol-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(3,5 -dimethyl- 1 ,2-oxazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-
2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-( 1 -isonicotinoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(pyridazin-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrimidin-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[3-(piperidin- 1 -yl)propanoyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(r-benzoyl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [6-(benzoylamino)hexyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-({4-[(benzoylamino)methyl]benzyl}carbamoyl)phenyl]-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [4-(5-oxo-L-prolyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(5-oxo-D-prolyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[(l -acetylpiperidin-4-yl)carbonyl]piperazin-l -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(2-acetamidobenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[4-(methylsulfonyl)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-butyrylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(4-isobutyrylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(2-methylbutanoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3,3,3-trifluoropropanoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(methoxyacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[4-(tetrahydrofuran-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(cyclopentylacetyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(cyclohexylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(2-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [4-(2-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(3-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[3-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {4-[4-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(3,4-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(3,5-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 4 - [(3 ,4 -dimethoxyphenyl) acetyl] piperazin- 1 -yl } phenyl)- 1 , 3 -dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(2-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(3-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[4-(lH-pyrrol-2-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(lH-pyrazol-5-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [4-(pyridin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(pyridin-3-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-isonicotinoylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyridazin-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrazin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrimidin-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide; N-{4-[4-(N,N-dimethyl-beta-alanyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-acetylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[4-(2-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(phenylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(l,3-thiazol-4-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(morpholin-4-ylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -oxo-2, 3-dihydro-lH-isoindol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)cyclohex-3 -en- 1 -yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[l -(3-methylbutyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[l -(2-phenylethyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N5-[2-(dimethylamino)ethyl]-N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {benzyl[3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(isobutoxycarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-bromo-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
methyl 4-{ [(5-cyano-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoate; N-(4- { (E)-[(benzyloxy)imino]methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-hydroxy-4-methylpentan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-aminopyrrolidin-l-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-{6-[(3-methylbutyl)carbamoyl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(3-phenylpropyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{ 6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2,5- dicarboxamide;
N-[4-({benzyl[3-(morpholin-4-yl)propyl] amino }methyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(pyridin-3-yl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -methyl- lH-pyrazol-4-yl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-methoxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-hydroxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(aminomethyl)-N- { 4-[(cyclopentylacetyl)amino]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-(methylthio)butan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2S,3S)-1 -hydroxy-3-methylpentan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S,3R)-l,3-dihydroxybutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xyhexan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-1 -hydro xypentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S,2S)-2-hydroxycyclopentyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { [( 1 S ,2R) -2-hydroxycyclopentyl] carb amoyl } phenyl) -1,3 -dihydro -2H-isoindole- 2-carboxamide;
N-(4- { [(2S)- 1 -cyclohexyl-3-hydroxypropan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide; N-[4-({ (2R)- 1 -hydroxy-3-[(4-methylbenzyl)thio]propan-2-yl }carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(IS)- 1 -(4-tert-butylphenyl)-2-hydroxyethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methoxy- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-(pyridin-4-yl)- 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(3-methylbutyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-[l -(3-methylbutyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-{ 5-[(3-methylbutyl)carbamoyl]pyrazin-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { 1 - [(2-methoxyethoxy)acetyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { ( 1 E) -3 - [benzyl(methyl) amino]prop- 1 -en- 1 -yl } phenyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(4-phenoxypiperidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(3-phenoxyazetidin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [benzyl(methyl)amino] methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5,6-dihydroirnidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide; N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1H- 1 ,2,3-triazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[2-(2-oxopyrrolidin-l-yl)ethyl]-lH-l,2,3-triazol-4-yl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(l-benzylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-phenylpropyl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ l-[4-(morpholin-4-yl)benzyl]-lH-l,2,3-triazol-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-isobutyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(cyclopentylmethyl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methoxypropyl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { 1 -[(2-memoxyemoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{5-[l-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]pyridin-2-yl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-3-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4- { [(2 -methoxyethoxy) acetyl] amino jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(l'-isobutyryl-l',2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(l'-benzoyl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-2-ylacetyl)amino]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide; N-{ 4-[(ethoxyacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-(hydroxymethyl)-N-{4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-{4-[(moφholin-4-ylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- 1 -dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[l'-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-2,4'- bipyridin-5-yl } - 1 -dinydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 -dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 -dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- l,3-dihydro-2H-isoindole-2-carboxamide; N-[l'-(l,4-dioxan-2-ylcarbonyl)-1^2^3^6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ r-[(l-methylpyrrolidin-3-yl)carbonyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}- l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 1 '-[( 1, 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-2,4'- bipyridin-5 -yl } - 1 , 3 -dihydro-2H-isoindole-2 -carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(azetidin- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(propyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(2-methoxyethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide; N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide; N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(morpholin-4-ylmethyl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{5-[(4-methylpiperazin-l-yl)methyl]-l,2,4-oxadiazol-3-yl Jphenyl)- 1,3-dihydro-
2H-isoindole-2-carboxamide;
N-[4-(5- { [(3-methylbutyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- {5-[(4-hydroxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { Γ- [( 1 -methylpyrrolidin-3-yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3 ,4'-bipyridin-6-yl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3,4'- bipyridin-6-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [3-(dimethylamino)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [4-(2-aminoethyl)- lH-imidazol- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(dimemylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(pyrimidin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-methoxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-[4-({ [(4S)-2,2-dimethyl- 1 ,3-dioxolan-4-yl]methyl }carbamoyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ [(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methyljcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino } -2-oxoethyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(3- {benzyl[3-(morpholin-4-yl)propyl] amino } -3-oxopropyl)phenyl] - 1 ,3-dihydro-
2H-isoindole-2-carboxamide; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2R)-butan-2-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4- cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methyl- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(morpholin-4-ylacetyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[l'-(morpholin-4-ylacetyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(2- { (4-fluorobenzyl)[4-(pyridin-3-yl)benzyl]amino } - 1 ,3-thiazol-5-yl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2 -benzyl- 1 ,3-thiazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-methylbutyl)sulfamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; 5-cyano-N- { 4-[(cyclopentylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- { 4-[(l ,3-thiazol-5-ylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1R) -3 -hydroxy- 1 -phenylpropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(4-methylphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide; 5-cyano-N- { 4-[(l ,3-dihydroxypropan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2R)-l-hydroxy-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2-(4-methylpiperazin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyljcarbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(4-hydroxybutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(3-furylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- {4-[(tetrahydro furan-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(2-furoyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yljcarbonyl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(ethylsulfonyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- {4-[(tetrahydro furan-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(lR)-2-hydroxy-l -phenylethyljcarbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; 5-cyano-N-(4- { [(2S)- 1 -hydro xybutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2,3-dihydroxypropyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(pyridin-2-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(l -hydroxy-4-methylpentan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N-(5-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyljpyridin-2-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.3]hept-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.4]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-13-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,9-diazaspiro[5.5]undec-3-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- {benzyl[3-(morpholin-4-yl)propyl] amino } -4-oxobutyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino }emyl)phenyl]- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-acetyl-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl } phenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -hydroxy ethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(butyrylamino)phenyl] -5-cyano- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3-methoxybenzyl)sulfonyl]amino jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2, 8 -diazaspiro [4.5] dec-2 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2,7 -diazaspiro [4.5] dec-7 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 8 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-[4-(2-oxa-7-azaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-(acetamidomethyl)-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{5-[2-(2-chlorobenzyl)-l,3-thiazol-4-yl]-2-thienyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydro-2H-pyran-4-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(2-hydroxypropan-2-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl {4-[(13-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzyl}carbamate;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(methoxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(5- { [(tetrahydrofuran-2-ylmethyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- {5-[(4-methoxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl } phenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(5- { [4-(2-methoxyethyl)piperazin- 1 -yl]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [l-(morpholin-4-yl)cyclopentyl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-pentanoylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 -acetylpiperidin-4-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butyrylpiperidin-4-yl)oxy]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4-{ [l-(3,3 -trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-4-yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[( 1 -acetylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [( 1 -isobutyrylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [ 1 -(3-methylbutanoyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxyjpyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(methoxyacetyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopropylacetyl)piperidin-4-yl]oxyjpyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-(6 - { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl] oxy } pyridin-3 -yl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopentylacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl (2- { 4- [( 1 ,3-dihydro-2H-isoindol-2- ylc arbonyl) amino] phenyl } ethyl)c arb amate ;
N-(4-{ l-[(2R)-tetr ahydrofuran-2-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(lS)-l-(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-cyano-N- { 4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(3 -phenylpropanoyl)pyrrolidin- 3 -yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- [4 -( { 1 - [(4-methoxyphenyl) acetyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)pyrrolidin-3 -yl] oxy } phenyl) -1,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-benzoylpyrrolidin-3-yl)oxy]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -( { 1 - [( 1 -methylcyclopropyl)carbonyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -acetylpyrrolidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine- 2-carboxamide;
N-(4- { [ 1 -(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethoxyacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ 1-[(1 -methylpiperidin-4-yl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
tert-butyl [( 1 - { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } azetidin-3- yl)methyl]carbamate;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(morpholin-4-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2-methoxyethoxy)acetyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(2,3-dimethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide; N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2,2-dimethylpropanoyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tricyclo[3.3.1.1~3,7~]dec-l-ylacetyl)azetidin-3-yl]oxyjphenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [(4-methoxycyclohexyl)carbonyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [4-(acetylamino)phenyl] sulfonyl } amino)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(propylsulfonyl)aminojphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-propylphenyl)sulfonyl]amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(butylsulfonyl)aminojphenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine-2- carboxamide;
N-{4-[({ [(lS,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-l- yljmethyl } sulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(ethylsulfonyl)aminojphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(benzylsulfonyl)amino]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N-(4- { [(4-fluorophenyl)sulfonyl] amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(thiophen-2-ylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,6-diazaspiro[3.5]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(Ν,Ν-dimethylglycyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l-en-l-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] amino } cyclohex- 1 -en- 1 - yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(4,4-difluorocyclohexyl)carbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(piperidin-l-ylsulfonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; 5-fluoro-N-(4-{ [l-(l,3-thiazol-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4,4-difluorocyclohexyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- lH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5-fluoro- l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-D- phenylalanin amide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl}phenyl)-5- fluoro-l,3-dihydro-2H-isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl} -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(3,5 -dimethyl- lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5-fluoro- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(5-methyl-lH-pyrazol-l-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-chloro-lH-pyrazol-l-yl)ethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-5,7- dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide; N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-carbamoylbenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 ,7-dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
Nalpha-{4-[(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-ylcarbonyl)amino]benzoyl}-L- phenylalanin amide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl }phenyl)-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5,7-dihydro-6H-pyrrolo [3 ,4- b]pyridine-6-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-[4-(4,5,6,7-tetrahydro-lH-indazol-5-ylcarbamoyl)phenyl]-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [(3-methyl- 1 ,2-oxazol-5-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -cyanobutan-2-yl]carbamoyl}phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[methyl(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrazol-3-yl)methyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- {4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(l -methoxybutan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } -5-fluoro- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl} -5-fluoro- l,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(pyridin-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropyle thy 1] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(l-methylcyclopropyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(miophen-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(4-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrrol-2-yl)methyl] carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyljphenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-l-amino-l-oxobutan-2-yl]carbamoyljphenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(lH-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl]-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-2-methylbutyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenylj - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5-fluoro-1 -dihydro-2H-isoindole-2-carboxarnide;
5-fluoro-N- { 4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)(methyl)carbamoyl]phenylj - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l-cyanoethyl)carbamoyl]phenylj-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenylj - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenylj-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-(4-{ [(3-memyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[memyl(3-methylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(l-memyl-lH-pyrazol-3-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [l-(l,3-thiazol-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{ 4-[( 1 -methoxybutan-2-yl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(4-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(2-ethoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{ 4-[( 1 -cyanocyclopropyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [2-(5-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(4-methyl-l,3-thiazol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide; N-{4-[(2-methylpropyl)carbamoyl]phenyl}-5 ,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(lR)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(thiophen-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [(1 S)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(l-memyl-lH-pyrrol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(dimemylarrdno)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -cyanoethyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[methyl(propyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b] pyridine-6-carboxamide;
methyl l-{4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } azetidine-3-carboxylate;
N-(4- { 3-[(3-methylbutyl)carbamoyl]azetidin- 1 -yl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydrofuran-2-ylmethyl)carbamoyl] azetidin- 1 -yljphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [3 -(benzylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c] pyridine-2-carboxamide;
N-{ 4-[3-(cyclopentylcarbamoyl)azetidin-l -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4- { 3-[(cyclopentylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3 - [(2-methoxyethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3-methylbutanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopentylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-2-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(pyrrolidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(pyrazin-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4,4-difluorocyclohexyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({2-[(dimethylamino)methyl]benzyl}carbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(1 -oxazol-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(furan-2-yl)-2-(pyrrolidin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydrofuran-3-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl }- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[( 1 -acetylpiperidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butanoylpiperidin-3 -yl)oxy] phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-3 -yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [3-(3,5 -dimethyl- IH-pyrazol- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 ,3 -thiazol-2-yl)ethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(2,2-difluoroethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(5-methyl-l, 2-oxazol-3-yl)methyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-4-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -L- phenylalanin amide;
N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(thiophen-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxarnide;
N-{ 4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-3-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(acetylamino)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -methoxybutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pyrimidin-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-( 1 H-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-methylbutyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4- { [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(1 -acetylpiperidin-4-yl)carbonyl] amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(ethoxyacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{4-[(bicyclo[2.2.1]hept-2-ylacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 ,3-thiazol-5-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(4-0X0-4, 5,6,7-tetrahydro-l-benzofuran-3-yl)carbonyl] amino jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {2-[(3-methylbutanoyl)amino]ethyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{2-[(4-methylpentanoyl)amino]ethyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(ethoxy acetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(2- { [(2-methoxyethoxy)acetyl] amino } ethyl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-2-ylcarbonyl) amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(cyclopentylcarbonyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(cyclopentylacetyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[2-(benzoylamino)emyl]phenyl}-l,3-dmydro-2H-isoindole-2-carboxarnide; N-(4-{2-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]ethyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydro-2H-pyran-4 -ylacetyl)amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-3 -ylacetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole-
2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 -propanoylazetidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2,2-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-ethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(pent-4-ynoyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-2-ylcarbonyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-3-ylcarbonyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(thiophen-3-ylcarbonyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)azetidin-3 -yljoxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethylglycyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethyl-beta-alanyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(pyrrolidin- 1 -ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(pyrrolidin-l-yl)propanoyl]azetidin-3-yl}oxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [3-(piperidin- 1 -yl)propanoyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[(4-methylpiperazin- 1 -yl)acetyl] azetidin- 3 -yl } oxy )phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(4-methylpiperazin-l-yl)propanoyl]azetidin-3-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopropylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopentylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3,3-dimethylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(butylsulfonyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylsulfonyl)piperidin-4-yl] oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-({ l-[(4-fluorophenyl)sulfonyl]piperidin-4-yl}oxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propan-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(benzylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-2-methylbutanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(4,4-difluorocyclohexyl)carbonyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-D-prolyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylpropanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpentanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-ethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4 - { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)piperidin-4-yl] oxy jphenyl) -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(l,2 -oxazol-5 -ylcarbonyl)piperidin-4-yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(pyridazin-3-ylcarbonyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(pyrazin-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-l,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(piperidin-l-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[3-(4-methylpiperazin- 1 -yl)propanoyl]piperidin-4-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
benzyl trans-3-[(l,3-dmydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl)amino]cyclobutanecarboxylate;
N-[4-(4- { [(4-methylpiperazin- 1 -yl)acetyl] amino jcyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(benzoylamino)cyclohex- 1 -en- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 -methylpiperidin-4-yl)carbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(1,1 -dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3R)-tetrahydrofuran-3-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3S)-tetrahydrofuran-3 -ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-2-methylbutanoyl]amino jcyclohex- 1 -en-1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{3-[(3 -methylbu tanoyl) amino] oxetan-3 -yl } phenyl) - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide; tert-butyl 4-({4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } sulfonyl)piperidine- 1 -carboxylate;
N-{ 4-[4-(propylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(2-methoxyethyl)carbamoyl]piperidin- 1 -yl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(cyclopentylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(l ,4-dioxan-2-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [4-(cyclopentylcarbamoyl)piperidin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [4-(tetrahydro-2H-pyran-4-ylcarbamoyl)piperidin- 1 -yljphenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(morpholin-4-ylcarbonyl)piperidin- 1 -yljphenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[4-(cyclopropylcarbamoyl)piperidin-l -yljphenyl} -l,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-hydroxy-2-methylpropyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(butan-2-ylcarbamoyl)piperidin- 1 -yljphenyl } -1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yljphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { (4R)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { (4S)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[trans-3-(benzylcarbamoyl)cyclobutyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{trans-3-[(2-phenylethyl)carbamoyl]cyclobutylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { trans-3- [(3-phenylpropyl)carbamoyl] cyclobutyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methyl- 1 ,3-oxazol-4-yl)carbonyl]- 1 ,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(furan-3-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-3-(furan-2-yl)prop-2-enoyl] -1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,3-oxazol-5-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3,3,3-trifluoropropanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,5 -dimethyl- 1 H-pyrazol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methoxycyclohexyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,3-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-difluorocyclopropyl)carbonyl] -1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(lH-pyrazol-5-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tert-butoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-l,2,4-triazol-l-yl)propanoyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(3-ethoxypropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-hydroxy-3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-pyrrol- l-yl)propanoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylcyclopropyl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methylpropoxy)acetyl] - 1 ,2, 3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 -methylprolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -hydroxycyclopropyl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l - { [1 -(methoxymethyl)cyclopropyl]carbonyl } - 1 ,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(methylsulfonyl)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -acetyl- 1 ,2, 3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[l -(cyclopropylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-4-methylpent-2-enoyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(2-methoxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopent- 1 -en- 1 -ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 - dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(thiophen-3-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -propanoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2,2-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrrol-2-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,2-dimethylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(4-methylhexanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-dimethylcyclopropyl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-5-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclobutylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(piperidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[2-(pyrrolidin- 1 -yl)propanoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2-methoxyethoxy)acetyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -(trans-4- { [(2 -methoxyethoxy) acetyl] amino } cyclohexyl)phenyl] -1,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(cis-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } eye lohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclone xyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3R)-l-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl] oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ (3R)- 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]pynolidin-3-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3R)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pynolidin-3-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-{6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridazin-3-yl}-1 -dmydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(bicyclo[2.2 ]hept-2-ylmethyl)carbamoyl]pyridazin-3-yl} -l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(2-methylpropanoyl)amino]cyclohexyl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(2-methylpropanoyl)amino]cyclohexyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(cyclohexylcarbonyl)amino]cyclohexyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(cyclohexylcarbonyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(cyclopropylacetyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(cyclopropylacetyl)amino]cyclohexyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(cyclopentylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l -en-1 -yljphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; and pharmaceutically acceptable salts thereof.
Embodiments of Formula (IIIc)
In another aspect, the present invention provides compounds of Formula (IIIc)
Figure imgf000427_0001
(IIIc);
and pharmaceutically acceptable salts thereof; wherein X1, X2, X3, are as described herein for Formula (Ic); and Rx is as described herein for substituents at the para position in Formula (Ic) when R2 is phenyl.
In one embodiment of formula (IIIc),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2,
C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2,
NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02,
N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
Rx is R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2,
NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5,
NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5,
NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5,
C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN,
N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl, wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when X1, X2, and X3 are CH; Rx is not methyl;
with the proviso that when X1, X2, and X3 are CH; Rx is not methoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (IIIc), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. Γη another embodiment of Formula (IIIc), X1, X2, and X3 are CH. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (IIIc), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (IIIc), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (IIIc), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (IIIc), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (IIIc), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (IIIc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IIIc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), R1 is C(0)NH2 In another embodiment of Formula (IIIc), R1 is F. In another embodiment of Formula (IIIc), R1 is CI. In another embodiment of Formula (IIIc), R1 is Br. In another embodiment of Formula (IIIc), R1 is CN. In another embodiment of Formula (IIIc), R^s NH2. In another embodiment of Formula (IIIc), R1 is N02. In another embodiment of Formula (IIIc), R1 is CF3. In another embodiment of Formula (IIIc), R1 is C(0)OH. In another embodiment of Formula (IIIc), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is
CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2,
NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or
OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR^ R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or
OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2 In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and RHs NH2. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (IIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (IIIc), X1 is CH; and
X 2z and X 3J are CR 1 ; and R1 is C(0)R 3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In one embodiment of formula (IIIc), Rx is R5, OR5, S02R5, C(0)R5, CO(0)R5, NHR5, NHC(0)R5, NHS(0)2R5, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOR5, S02NHR5 or CF3. In another embodiment of formula (IIIc), Rx is R5, and R5 is heterocyclyl, which is optionally substituted as described in embodiments herein.
In another embodiment of Formula (IIIc), Rx is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-l(2H)-onyl, 5-fluorophthalazin-l(2H)- onyl, (Z)-3H-benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2-d][l,2,4]triazin-l(2H)-one, isoindolin-l-onyl, or 1,2,3,6-tetrahydropyridinyl. In another embodiment of Formula (IIIc), Rx is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin- 1 (2H)-onyl, 5,6,7,8-tetrahydrophthalazin- 1 (2H)-onyl, 5-fluorophthalazin- 1(2H)- onyl, (Z)-3H-benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, isoindolin- 1 -onyl, or pyrrolo [ 1 ,2-d] [ 1 ,2,4] triazin- 1 (2H)-one; which are optionally substituted as defined herein. In another embodiment of Formula (IIIc), Rx is ,2,3,6-tetrahydropyridinyl; which is optionally substituted as defined herein.
Still another embodiment pertains to compounds having Formula (IIIc), which include
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(aminomethyl)benzyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(furo[3,2-c]pyridin-4-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(pyridin-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] -5-fluoro- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(thieno[3,2-c]pyridin-4-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(2,3-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4- [(3 -phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [4-(pyridazin-3-yl)piperazin-l-yl]carbonyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2,3-dihydro- 1 ,4-benzodioxin-5-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(3-methylbutyl)-lH-pyrazol-4-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(3-methylbutyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-fluorobenzyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(2-oxopyrrolidin-l-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-methyl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(4-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-fluoro-5-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [4-(pyrazin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-methoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [4-(pyrimidin-2 -yl)piperazin- 1 -yl] carbonyl } phenyl) -1,3 -dihydro-2H-isoindole- 2-carboxamide;
5-nitro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-fluorophenyl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(2-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(3-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(4-acetylphenyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(2,3-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-thienylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-thienyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; 4-chloro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4-phenylpiperazin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(6-aminohexyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide;
4-chloro-N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 ,3-benzodioxol-5-ylmethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-3-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridazin-3-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(3-fluorophenyl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl }phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3-butoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [2-(3,4-dihydroxyphenyl)ethyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-propoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-furylmethyl)carbamoyl]phenyl}-1 -dinydro-2H-isoindole-2-carboxarnide; N-(4- { [4-(2-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(3-hydroxy-2-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)carbamoyl]phenyl}-5-(trifluoromethyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methyl-lH-indazol-5-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5-(trifluoromethyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(2,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
methyl 5-({4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl} amino)- 1H- indazole-3-carboxylate;
N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(5-chloropyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-indol-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethyl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole -2- carboxamide;
N-{4-[(3,5-dimethoxyphenyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro- 1 ,4-benzodioxin-6-ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(2-fluorobenzoyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [2-(5-methoxy- lH-indol-3-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-propoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-4-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- [4 -( { 2- [4-(dimethylamino)phenyl] ethyl } carbamoyl)phenyl] -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(4-{ [3-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(lR)-3-hydroxy- 1 -phenylpropyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-fluoro-4-methoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(l ,3-benzodioxol-5-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(2-methoxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(2-isopropoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-methoxypropyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-fluorophenyl)emyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxamide; N- { 4- [(2-phenoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(4-hydroxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 1 - [(3S)-tetrahydrofuran-3 -yl] - 1 H-pyrazol-4-yl } carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(2-phenylethyl)carbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(2,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(methylthio)propyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-ethoxyethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 4-[(trifluoromethyl)thio]benzyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-fluorophenyl)pyrrolidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(lH-imidazol-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(hydroxymethyl)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-benzodioxol-5-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -isopropyl- lH-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[methyl(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(thiomoφholin-4-ylcarbonyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxarnide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4-{ [4-(2-furoyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzylpiperidin-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(5-acetamido-2-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(3,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ 2-[3-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-( 1 H-imidazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1R)- 1 -(3-cyanophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [benzyl(2-hydroxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-cyanophenyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(4-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(pyridin-2-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyanomethyl)carbamoyljphenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclohexylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[butyl(methyl)carbamoyl]phenyl}-13-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [4-(dimethylamino)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,4-dihydroisoquinolin-2(lH)-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro-lH-indol-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(phenylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(diethylamino)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-hydroxy-2-phenylethyl)(methyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-aminophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
tert-butyl (1 - { 4-[( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl }piperidin-4- yl)carbamate;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 4- [3-chloro-5 -(trifluoromethyl)pyridin-2-yl]piperazin- 1 -yl } carbonyl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(cyclohexylmethyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(3-chlorobenzyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(diethylcarbamoyl)piperidin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-hydroxyethyl)piperazin-l -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N- { 4- [(2-hydroxy-6-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-hydroxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5,6-dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(5-fluoropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopropylmethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3,4,9-tetrahydro-2H-beta-carbolin-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tert-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({ 4-[4-(trifluoromethyl)phenyl]piperazin- 1 -yl}carbonyl)phenyl] - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N- { 4- [(3-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,3-difluoropyrrolidin- 1 -yl)carbonyl]phenyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(3S)-1 -benzylpyrrolidin-3-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-carbamoylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopropylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(methylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(dimethylamino)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(pentan-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentan-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclobutylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[( 1 ,3-dioxolan-2-ylmethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(4-fluorophenyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l -phenyl- lH-pyrazol-4-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 2-[4-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methoxyethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(sec-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[bis(2-ethoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [butyl(ethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [isobutyl(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-carbamoylphenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(2S)-2-(trifluoromethyl)pyrrolidin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-methylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[ethyl(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,6-dimethylmorpholin-4-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(prop-2-yn- 1 -ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole -2-carboxamide; N-{4-[isopropyl(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[isopropyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-cyanoethyl)(cyclopropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[emyl(isopropyl)carbamoyl]phenyl}-13-dmydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-fluoropyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -N-isopropyl-beta- alanine;
N-{4-[methyl(propyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; 5,6-dimethoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [3-(4-chlorophenoxy)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethoxy)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-phenyl-l,3-thiazol-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
methyl 2- { [4-(propylcarbamoyl)phenyl] carbamoyl } isoindoline-5-carboxylate;
2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid;
5-amino-N- [4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; 5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-(aminomethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(2-hydroxy-2-methylpropanoyl)amino] -N- [4-(propylcarbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(N,N-dimethylglycyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-[(methylsulfonyl)amino] -N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(4,4,4-trifluorobutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(4-phenylbutanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-methylpentanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [(benzyloxy)acetyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenylpropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(3-phenoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [N-(2-furoyl)glycyl] amino jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(2-thienyl)butanoyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-oxo-4-phenylbutanoyl)amino]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(N-benzoylglycyl)amino]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[(4-phenoxybutanoyl)amino]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(propionylamino)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(hexanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(heptanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pent-4-enoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(ethoxyacetyl)aminojphenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2-methoxyethoxy)acetyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyclopropylacetyl)aminojphenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [3-(4-methylpiperazin-l -yl)propanoyl] amino jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5- carboxylate;
2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-cyclopentylethyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6- dihydropyridine- 1 (2H)-carboxylate;
N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -methyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [( 1 E)-5-phenylpent- 1 -en- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -propyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(l -benzyl- lH-pyrazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(2-hydroxyethyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- [4 -(5 -phenylpentyl)phenyl] -1,3 -dihydro-2H-isoindole-2 -carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [ 1 -(isopropylsulfonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-benzoylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole -2-carboxamide;
N- { 4- [4-(isopropylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(phenylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(benzoylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [3 -(butyrylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperazine- 1 - carboxylate;
N-[4-(4-propionylpiperazin-l-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-(cyclopropylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexyloxy)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isoquinolin-4-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4, 5,6,7, 8-hexahydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-
2-carboxamide;
N-[4-(8-fluoro-4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
5-fluoro-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -5-(pyrrolidin- 1 -ylmethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-(morpholin-4-ylmethyl)-N-[4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-methoxy-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- [(4-methylpiperazin- 1 -yl)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-[4-(l -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-chloro-N- [4-( 1 -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-4,5-dihydro-3H-2,3-benzodiazepin-l-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]-5-(pyrrolidin-l -ylmethyl)- 1,3- dihydro-2H-isoindole-2-carboxamide; N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(4-methylpiperazin-l-yl)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } -5-(pyrrolidin- 1 - ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-[(l -methylpiperidin-4-yl)oxy] -N- [4-(4-oxo-3,4-dihydrophthalazin-l -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-{ [(3R)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-{ [(3S)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(azetidin- 1 -ylmethyl)-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperidine- 1 - carboxylate;
N-[4-(5-propyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(piperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-butyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -isobutyrylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[5-(3-methylbutyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(5-benzyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3R)-tetrahydrofuran-3-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(5-chloropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-hydroxy-4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-oxopyrrolidin- 1 -yl)benzyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ [(lS,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(l-hydroxycyclopropyl)methyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl] -5-vinyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-benzoylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(tetrahydrofuran-3-yl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide; N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- d]pyrimidine-6-carboxamide;
N-(4-{ [(3-phenylpropyl)amino]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- d]pyrimidine-6-carboxamide;
N-{4-[l-(4-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -benzyl- 1,2,3, 6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(tetrahydrofuran-3-ylmethyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2S)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2R)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [( 1 S) -2-hydroxy- 1 -phenylethyl] amino } carbonyl)phenyl] -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [4-(2-methoxyethyl)piperazin-l -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-2-(2-hydroxyethyl)piperidin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-3-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-4-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N5-(2-methoxyethyl)-N2-{4-[(propylamino)carbonyl]phenyl}-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N-(4-cyanophenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(trifluoromethyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4 - { [(tetrahydrofuran-3 -ylmethyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-pyridin-2-ylpiperazin-l-yl)carbonyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
5-( 1 ,2-dihydroxyethyl)-N- { 4- [(propylamino)carbonyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(5-oxo-D-prolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -propionyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [ 1 -(2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(ethoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(2-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(3-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide; N-{4-[l-(4-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(4-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(4-chlorobenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[3-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[4-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(3-furoyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H-isoindole-
2-carboxamide;
N-{ 4-[l -(3-thienylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(lH-pyrrol-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2,5 -dimethyl- lH-pyrrol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,3-thiazol-4-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(lH-pyrazol-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(3,5 -dimethyl- 1 ,2-oxazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-( 1 -isonicotinoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(pyridazin-3-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide; N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrimidin-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[3-(piperidin- l-yl)propanoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [6-(benzoylamino)hexyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[(benzoylamino)methyl]benzyl}carbamoyl)phenyl]-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [4-(5-oxo-L-prolyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(5-oxo-D-prolyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[(l -acetylpiperidin-4-yl)carbonyl]piperazin-l -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(2-acetamidobenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[4-(methylsulfonyl)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-butyrylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(4-isobutyrylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [4-(2-methylbutanoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3,3,3-trifluoropropanoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(methoxyacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[4-(tetrahydrofuran-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N- { 4- [4-(cyclopentylacetyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(cyclohexylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(2-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(2-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[3-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {4-[4-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(3,4-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(3,5-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 4 - [(3 ,4 -dimethoxyphenyl) acetyl] piperazin- 1 -yl } phenyl)- 1 , 3 -dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(2-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(3-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[4-(lH-pyrrol-2-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(lH-pyrazol-5-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide; N- { 4- [4-(pyridin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(pyridin-3-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-isonicotinoylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyridazin-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrazin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrimidin-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(N,N-dimethyl-beta-alanyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-acetylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-(2-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(phenylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(l,3-thiazol-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(morpholin-4-ylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -oxo-2, 3-dihydro- lH-isoindol-4-yl)phenyl]- 1, 3-dihydro-2H-iso indole-2- carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N5- [2-(dimethylamino)ethyl] -N2- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{benzyl[3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(isobutoxycarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
5-bromo-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
methyl 4-{ [(5-cyano-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoate; N-(4- { (E)-[(benzyloxy)imino]methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-hydroxy-4-methylpentan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-aminopyrrolidin-l-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N2- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2,5- dicarboxamide;
N-[4-({benzyl[3-(morpholin-4-yl)propyl] amino }methyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(pyridin-3-yl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -methyl- lH-pyrazol-4-yl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-methoxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-hydroxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(aminomethyl)-N- { 4-[(cyclopentylacetyl)amino]phenyl} - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-(methylthio)butan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2S,3S)-1 -hydroxy-3-methylpentan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S,3R)-1, 3-dihydroxybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xyhexan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-1 -hydro xypentan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S,2S)-2-hydroxycyclopentyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { [( 1 S ,2R) -2-hydroxycyclopentyl] carb amoyl } phenyl) -1,3 -dihydro -2H-isoindole- 2-carboxamide;
N-(4- { [(2S)- 1 -cyclohexyl-3-hydroxypropan-2-yl] carbamoyl jphenyl)- 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
N-[4-({(2R)-l-hydroxy-3-[(4-methylbenzyl)thio]propan-2-yljcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide; N-(4- { [(IS)- 1 -(4-tert-butylphenyl)-2-hydroxyemyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methoxy- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-phenylethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-(pyridin-4-yl)- 1 ,3 -dihydro-2H-isoindole-
2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(3-methylbutyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { ( 1 E) -3 - [benzyl(methyl) amino]prop- 1 -en- 1 -yl } phenyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(4-phenoxypiperidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-phenoxyazetidin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [benzyl(methyl)amino] methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide; N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(piperidin-l -yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1H- 1 ,2,3-triazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[2-(2-oxopyrrolidin-l-yl)ethyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(l-benzylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-phenylpropyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ l-[4-(morpholin-4-yl)benzyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-isobutyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(cyclopentylmethyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[l-(3-methoxypropyl)-lH-l,2,3-triazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { 1 -[(2-memoxyemoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-3-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4- { [(2 -methoxyethoxy) acetyl] amino jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-2-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(ethoxyacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-(hydroxymethyl)-N-{4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-{4-[(moφholin-4-ylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(l-methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(azetidin- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(morpholin-4-ylmethyl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{5-[(4-methylpiperazin-l-yl)methyl]-l,2,4-oxadiazol-3-yl Jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(5-{ [(3-methylbutyl)amino]methyl}-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide; N-(4- {5-[(4-hydroxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [3-(dimethylamino)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [4-(2-aminoethyl)- lH-imidazol- 1 -yljcarbonyljphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yljcarbonyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide; N-(4- { [(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl]carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-methoxy- 1 -phenylethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ [(4S)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ [(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}carbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino } -2-oxoethyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(3- {benzyl[3-(morpholin-4-yl)propyl] amino } -3-oxopropyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2R)-butan-2-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methyl- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3-methyloxetan-3-yl)methyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2 -benzyl- l,3-thiazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-methylbutyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(cyclopentylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide; 5-cyano-N- { 4-[(l ,3-thiazol-5-ylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1R) -3 -hydroxy- 1 -phenylpropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(4-methylphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(l ,3-dihydroxypropan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2R)-l-hydroxy-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2-(4-methylpiperazin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyljcarbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(4-hydroxybutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- {4-[(3-furylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- {4-[(tetrahydro furan-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(2-furoyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yljcarbonyl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide; 5-cyano-N-(4- { [4-(ethylsulfonyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- {4-[(tetrahydro furan-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2S)-1 -hydro xybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2,3-dihydroxypropyl)carbamoyl]phenylj - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(pyridin-2-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(l -hydroxy-4-methylpentan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.3]hept-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.4]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(2,8-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,9-diazaspiro[5.5]undec-3-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- {benzyl[3-(morpholin-4-yl)propyl] amino } -4-oxobutyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(2-{benzyl[3-(morpholin-4-yl)propyl] amino }ethyl)phenyl]-l, 3-dihydro-2H- isoindole-2-carboxamide;
5-acetyl-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -hydroxy ethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(butyrylamino)phenyl] -5-cyano- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3-methoxybenzyl)sulfonyl]amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2, 8 -diazaspiro [4.5] dec-2 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2,7 -diazaspiro [4.5] dec-7 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 8 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(2-oxa-7-azaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-(acetamidomethyl)-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-( { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl] methyl } carbamoyl)phenyl] - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydro-2H-pyran-4-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(2-hydroxypropan-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl {4-[(13-dmydro-2H-isoindol-2-ylcarbonyl)amino]benzyl}carbamate; N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(methoxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(5- { [(tetrahydrofuran-2-ylmethyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- {5-[(4-methoxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl Jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(5- { [4-(2-methoxyethyl)piperazin- 1 -yl]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [l-(moφholin-4-yl)cyclopentyl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-pentanoylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 -acetylpiperidin-4-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butyrylpiperidin-4-yl)oxy]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide; N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-4-yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
tert-butyl (2- { 4- [( 1 ,3-dihydro-2H-isoindol-2- ylc arbonyl) amino] phenyl } ethyl)c arb amate ;
N-(4-{ l-[(2R)-tetr ahydrofuran-2-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyljphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyljcarbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-cyano-N- { 4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lS)-l-(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(3,3, 3-trifluoropropanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(cyclopentylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(3 -phenylpropanoyl)pyrrolidin- 3 -yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(phenylacetyl)pyrrolidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- [4 -( { 1 - [(4-methoxyphenyl) acetyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)pyrrolidin-3 -yl] oxy } phenyl) -1,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-benzoylpyrrolidin-3-yl)oxy]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(l -methylcyclopropyl)carbonyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -acetylpyrrolidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine- 2-carboxamide;
N-(4-{ [l-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(ethoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ 1-[(1 -methylpiperidin-4-yl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetrahydrofuran-3-ylcarbonyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
tert-butyl [( 1 - { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } azetidin-3- yl)methyl]carbamate;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(morpholin-4-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2-methoxyethoxy)acetyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [l-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(2,3-dimethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2,2-dimethylpropanoyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tricyclo[3.3.1.1~3,7~]dec-l-ylacetyl)azetidin-3-yl]oxyjphenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [(4-methoxycyclohexyl)carbonyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [4-(acetylamino)phenyl] sulfonyl } amino)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N- { 4- [(propylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-propylphenyl)sulfonyl]amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(butylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine-2- carboxamide;
N-{4-[({ [(lS,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-l- yl]methyl } sulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(ethylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(benzylsulfonyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-fluorophenyl)sulfonyl] amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(thiophen-2-ylsulfonyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,6-diazaspiro[3.5]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(Ν,Ν-dimethylglycyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l-en-l-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] amino } cyclohex- 1 -en- 1 - yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(4,4-difluorocyclohexyl)carbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(piperidin- 1 -ylsulfonyl)phenyl]- 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
5-fluoro-N-(4-{ [l-(l,3-thiazol-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(4,4-difluorocyclohexyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- lH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5-fluoro- l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-D- phenylalaninamide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide; N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-5-fluoro-13-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl}phenyl)-5- fluoro-l,3-dihydro-2H-isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-L- phenylalaninamide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl} -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3,5 -dimethyl- lH-pyrazol- 1 -yl)ethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(5-methyl-lH-pyrazol-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-chloro-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- IH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5, 7- dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-carbamoylbenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 ,7-dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
Nalpha-{4-[(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-ylcarbonyl)amino]benzoyl}-L- phenylalanin amide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl }phenyl)-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5,7-dihydro-6H-pyrrolo [3 ,4- b]pyridine-6-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-{4-[(3-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(4,5,6,7-tetrahydro-lH-indazol-5-ylcarbamoyl)phenyl]-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [(3-methyl- 1 ,2-oxazol-5-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -cyanobutan-2-yl]carbamoyl}phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(lH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrazol-3-yl)methyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [4-(dimethylamino)butyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(l -methoxybutan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } -5-fluoro- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl} -5-fluoro- l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(3-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(pyridin-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropyle thy 1] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(l-methylcyclopropyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4- [(thiophen-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(4-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro-
2H-isoindole-2-carboxamide; 5-fluoro-N-(4- { [(2S)- 1 -methoxypropan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrrol-2-yl)methyl]carbamoyl}phenyl)-l,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -amino- 1 -oxobutan-2-yl] carbamoyl }phenyl)-5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl]-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-2-methylbutyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5-fluoro-1 -dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N- { 4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[(l-cyanoethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carb amoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(3-methyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(1 -methyl- lH-pyrazol-3-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [4-(dimethylamino)butyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(l,3-thiazol-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -methoxybutan-2-yl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(2-ethoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide; N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(l-cyanocyclopropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [(4-methyl- 1 ,3-thiazol-2-yl)methyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-{4-[(2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(lR)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(thiophen-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [(1 S)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(l-memyl-lH-pyrrol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-(4-{ [3-(dimethylamino)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -cyanoethyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[memyl(propyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; methyl 1 - { 4- [( 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } azetidine-3-carboxylate;
N-(4- { 3-[(3-methylbutyl)carbamoyl]azetidin- 1 -yl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydrofuran-2-ylmethyl)carbamoyl] azetidin- 1 -yljphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [3 -(benzylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [3 -(cyclopentylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 3-[(cyclopentylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3 - [(2-methoxyethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopentylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-2-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(pyrrolidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4,4-difluorocyclohexyl)carbamo yljphenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({2-[(dimethylamino)methyl]benzyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,3-oxazol-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(furan-2-yl)-2-(pyrrolidin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydrofuran-3-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4- yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; 5-cyano-N- { 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl }- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[( 1 -acetylpiperidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butanoylpiperidin-3 -yl)oxy] phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-3 -yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [3-(3,5 -dimethyl- IH-pyrazol- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 ,3 -thiazol-2-yl)ethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(2,2-difluoroethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(5-methyl-l, 2-oxazol-3-yl)methyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [(1 -methyl- 1 H-pyrazol-4-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,5 -dimethyl- lH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -L- phenylalanin amide;
N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl] carbamoyl Jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(thiophen-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-3-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -methoxybutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pyrirnidin-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-( 1 H-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-methylbutyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(1 -acetylpiperidin-4-yl)carbonyl] amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(ethoxyacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [(tetrahydrofuran-2-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{4-[(bicyclo[2.2.1]hept-2-ylacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 ,3-thiazol-5-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(4-0X0-4, 5,6,7-tetrahydro-l-benzofuran-3-yl)carbonyl] amino jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {2-[(3-methylbutanoyl)amino]ethyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{2-[(4-methylpentanoyl)amino]ethyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(ethoxy acetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole-2- carboxamide; N-[4-(2- { [(2-methoxyethoxy)acetyl] amino } ethyl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-2-ylcarbonyl) amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(cyclopentylcarbonyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(cyclopentylacetyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[2-(benzoylamino)ethyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{2-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]ethyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydro-2H-pyran-4 -ylacetyl)amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-3 -ylacetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole- 2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 -propanoylazetidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-ethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(pent-4-ynoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)azetidin-3 -yl]oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]azetidin-3-yl}oxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethylglycyl)azetidin-3-yl]oxy Jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethyl-beta-alanyl)azetidin-3 -yljoxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrrolidin- 1 -ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(pyrrolidin-l-yl)propanoyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [3-(piperidin- 1 -yl)propanoyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[(4-methylpiperazin- 1 -yl)acetyl] azetidin-3-yl }oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(4-methylpiperazin-l-yl)propanoyl]azetidin-3-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopropylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopentylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3,3-dimethylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(2-methylpropyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(butylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylsulfonyl)piperidin-4-yl] oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(4-fluorophenyl)sulfonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propan-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(benzylsulfonyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-2-methylbutanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(4,4-difluorocyclohexyl)carbonyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-D-prolyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylpropanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpentanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-ethylbutanoyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4 - { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)piperidin-4-yl] oxy jphenyl) -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(l,2 -oxazol-5 -ylcarbonyl)piperidin-4-yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridazin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrazin-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(piperidin-l-yl)propanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[3-(4-methylpiperazin- 1 -yl)propanoyl]piperidin-4-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(4-methylpiperazin- 1 -yl)acetyl] amino jcyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(benzoylamino)cyclohex- 1 -en- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 -methylpiperidin-4-yl)carbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(1,1 -dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl] amino } cyclohex- 1 -en- 1 -yDphenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3R)-tetrahydrofuran-3-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(4- { [(3S)-tetrahydrofuran-3 -ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-2-methylbutanoyl]amino jcyclohex- 1 -en-1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 3 - [(3 -methylbu tanoyl) amino] oxetan-3 -yl } phenyl) - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
tert-butyl 4-({4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } sulfonyl)piperidine- 1 -carboxylate;
N-{ 4-[4-(propylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(2-methoxyethyl)carbamoyl]piperidin- 1 -yl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(cyclopentylmethyl)carbamoyl]piperidin- 1 -yl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{4-[(l,4-dioxan-2-ylmethyl)carbamoyl]piperidin-l-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [4-(cyclopentylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [4-(tetrahydro-2H-pyran-4-ylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(morpholin-4-ylcarbonyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[4-(cyclopropylcarbamoyl)piperidin-l-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]piperidin- 1 -yl } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-hydroxy-2-methylpropyl)carbamoyl]piperidin- 1 -yl } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(butan-2-ylcarbamoyl)piperidin- 1 -yl]phenyl } -1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yl}phenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { (4R)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { (4S)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methyl- 1 ,3-oxazol-4-yl)carbonyl]- 1 ,2,3, 6-tetr ahydropyridin-4- yljphenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(furan-3-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenylj-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-3-(furan-2-yl)prop-2-enoyl] -1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,3-oxazol-5-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenylj-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3,3,3-trifluoropropanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenylj-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,5 -dimethyl- 1 H-pyrazol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yljphenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methoxycyclohexyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,3-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2,2-difluorocyclopropyl)carbonyl] -1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(lH-pyrazol-5-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenylj -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tert-butoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-l,2,4-triazol-l-yl)propanoyl]-l,2,3,6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(3-ethoxypropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-hydroxy-3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-pyrrol- l-yl)propanoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylcyclopropyl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methylpropoxy)acetyl] - 1 ,2, 3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 -methylprolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -hydroxycyclopropyl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l - { [1 -(methoxymethyl)cyclopropyl]carbonyl } - 1 ,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(methylsulfonyl)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -acetyl- 1 ,2, 3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[l -(cyclopropylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-4-methylpent-2-enoyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(2-methoxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopent- 1 -en- 1 -ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 - dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(thiophen-3-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -propanoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2,2-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrrol-2-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,2-dimethylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(4-methylhexanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-dimethylcyclopropyl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-5-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclobutylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(piperidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[2-(pyrrolidin- 1 -yl)propanoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2-methoxyethoxy)acetyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -(trans-4- { [(2 -methoxyethoxy) acetyl] amino } cyclohexyl)phenyl] -1,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(cis-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } eye lohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclone xyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3R)-l-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl] oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ (3R)- 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3R)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pynolidin-3-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(2-methylpropanoyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(2-methylpropanoyl)amino]cyclohexyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(cyclohexylcarbonyl)amino]cyclohexyljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(cyclohexylcarbonyl)aminojcyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { trans-4- [(cyclopropylacetyl)amino]cyclohexyl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {cis-4-[(cyclopropylacetyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(cyclopentylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l -en-1 -yljphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; and pharmaceutically acceptable salts thereof.
Still another embodiment pertains to compounds having Formula (IIIc), which include
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(isoquinolin-4-yl)phenyl]-1 -dmydro-2H-isoindole-2-carboxarnide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4, 5,6,7, 8-hexahydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(8-fluoro-4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
5-fluoro-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -5-(pyrrolidin- 1 -ylmethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-(morpholin-4-ylmethyl)-N-[4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide; 5-methoxy-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- [(4-methylpiperazin- 1 -yl)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-
2-carboxamide;
5-chloro-N- [4-( 1 -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-4,5-dihydro-3H-2,3-benzodiazepin-l-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -5 -(pyrrolidin- 1 -ylmethyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(4-methylpiperazin-l-yl)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } -5 -(pyrrolidin- 1 - ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-[(l -methylpiperidin-4-yl)oxy] -N- [4-(4-oxo-3,4-dihydrophthalazin-l -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-{ [(3R)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-{ [(3S)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(azetidin- 1 -ylmethyl)-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide; and N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dmydro-2H-isoindole-2-carboxarnide;
N-[4-(l-oxo-2 -dmydro-lH-isoindol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)cyclohex-3 -en- 1 -yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-5-(pyrrolidin-l- ylmemyl)-l,3-dmydro-2H-isoindole-2-carboxarnide; and pharmaceutically acceptable salts thereof.
Embodiments of Formula (IVc)
In )
Figure imgf000509_0001
(IVc);
and pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (Ic).
In one embodiment of formula (IVc),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N; R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, andR10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R , NR13C(0)R , NHS(0)2R , NR13S(0)2R , NHC(0)OR , NR13C(0)OR , NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I; R , at each occurrence, is independently selected alkyl; wherein the R alkyl is optionally substituted with one, two, three or four alkoxy;and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (IVc), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (IVc), X1, X2, and X3 are CH. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (IVc), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (IVc), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (IVc), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (IVc), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (IVc), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (IVc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), R1 is C(0)NH2 In another embodiment of Formula (IVc), R1 is F. In another embodiment of Formula (IVc), R1 is CI. In another embodiment of Formula (IVc), R1 is Br. In another embodiment of Formula (IVc), R1 is CN. In another embodiment of Formula (IVc), R^s NH2. In another embodiment of Formula (IVc), R1 is N02. In another embodiment of Formula (IVc), R1 is CF3. In another embodiment of Formula (IVc), R1 is C(0)OH. In another embodiment of Formula (IVc), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc),
X 11 and X3J are CH; and X 2 is CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1 ; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6,
N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IVc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2 In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and RHs NH2. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (IVc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR^ R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2 In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (IVc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (IVc), which include
N- { 4-[(4,4,4-trifluorobutanoyl)amino]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(4-phenylbutanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-methylpentanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [(benzyloxy)acetyl]amino}phenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(3-phenylpropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [N-(2-furoyl)glycyl]arrdno}phenyl)-l,3-dmydro-2H-isoindole-2-carboxarnide; N-(4-{ [4-(2-thienyl)butanoyl]amino}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(4-oxo-4-phenylbutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(N-benzoylglycyl)amino]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-{4-[(4-phenoxybutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(propionylamino)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(hexanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(heptanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pent-4-enoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(ethoxyacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2-methoxyethoxy)acetyl]amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyclopropylacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [3-(4-methylpiperazin-l-yl)propanoyl] amino jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5- carboxylate;
2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2,5- dicarboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(pyridin-3-yl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -methyl- lH-pyrazol-4-yl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-methoxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-hydroxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide; 5-(aminomethyl)-N- { 4-[(cyclopentylacetyl)amino]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methoxy- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-(pyridin-4-yl)- 1 ,3 -dihydro-2H-isoindole-
2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-3-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4- { [(2 -methoxyethoxy) acetyl] amino } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-2-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(ethoxyacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-(hydroxymethyl)-N-{4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-{4-[(morpholin-4-ylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methyl- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-acetyl-N-{4-[(cyclopentylacetyl)arnino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -hydroxy ethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(butyrylamino)phenyl]-5-cyano-l,3-dihydro-2H-isoindole-2-carboxamide; -4-yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; 5-(acetamidomemyl)-N-{4-[(cyclopentylacetyl)amino]phenyl}-1 -dmydro-2H- isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(2-hydroxypropan-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dmydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(methoxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(1 -acetylpiperidin-4-yl)carbonyl] amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(ethoxyacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(tetrahydrofuran-2-ylcarbonyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{4-[(bicyclo[2.2 ]hept-2-ylacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 ,3-thiazol-5-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(4-0X0-4, 5,6,7-tetrahydro-l-benzofuran-3-yl)carbonyl] amino jphenyl)- 1,3- dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Embodiments of Formula (Vc)
In c)
Figure imgf000519_0001
(Vc); and pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R5 are as described herein for Formula (Ic).
In one embodiment of formula (Vc),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2,
C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH,
C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9,
S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF?CF3, F, CI, Br or I; R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R , OR , SR , S(0)R , S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl, wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In one embodiment of Formula (Vc), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (Vc), X1, X2, and X3 are CH. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (Vc), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (Vc), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (Vc), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (Vc), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (Vc), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (Vc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2,
C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), R1 is OR3; wherein R3 is alkyl, alkenyl, or
heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), R1 is C(0)NH2 In another embodiment of Formula (Vc), R1 is F. In another embodiment of Formula (Vc), R1 is CI. In another embodiment of Formula (Vc), R1 is Br. In another embodiment of Formula (Vc), R1 is CN. In another embodiment of Formula (Vc), R^s NH2. In another embodiment of Formula (Vc), R1 is N02. In another embodiment of Formula (Vc), R1 is CF3. In another embodiment of Formula (Vc), R1 is C(0)OH. In another embodiment of Formula (Vc), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X 11 and X3J are CH; and X 2 is CR 1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (Vc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc),
X 2z and X 3J are CH; and X 1 is CR1 ; R1 is R3 ; wherein R 3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is
CR1; and R1 is C(0)OH. In another embodiment of Formula (Vc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is
R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (Vc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (Vc), which include N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(aminomethyl)benzyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N- { 4-[(pyridin-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] -5-fluoro- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4- [(3 -phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2,3-dihydro- 1 ,4-benzodioxin-5-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(3-methylbutyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- {4-[(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(2-oxopyrrolidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-methyl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N- { 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-fluoro-5-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; 5-methoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-nitro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; 5-methyl-N-{4-[(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(2,3-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; 5-methoxy-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-thienyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(6-aminohexyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide;
4-chloro-N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 , 3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 ,3-benzodioxol-5-ylmethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(3-butoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(3,4-dihydroxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-propoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-furylmethyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide; N- { 4- [(3-hydroxy-2-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)carbamoyl]phenyl}-5-(trifluoromethyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[(3-memyl-lH-indazol-5-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,5-dimethoxyphenyl)ethyl]carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
methyl 5-({4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl} amino)- 1H- indazole-3-carboxylate;
N-(4- { [2-(2-oxopyrrolidin- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(lH-indol-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,5-dimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro- 1 ,4-benzodioxin-6-ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(5-methoxy- lH-indol-3-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(2-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-propoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [(4-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- [4 -( { 2- [4-(dimethylamino)phenyl] ethyl } carbamoyl)phenyl] -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(4-{ [3-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(lR)-3-hydroxy- 1 -phenylpropyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-fluoro-4-methoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(l ,3-benzodioxol-5-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(2-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-isopropoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-methoxypropyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxamide; N- { 4- [(2-phenoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-hydroxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 1 - [(3S)-tetrahydrofuran-3 -yl] - 1 H-pyrazol-4-yl } carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-phenylethyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(methylthio)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-ethoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 4-[(trifluoromethyl)thio]benzyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-(lH-imidazol-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(3-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(hydroxymethyl)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-benzodioxol-5-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [( 1 -isopropyl- lH-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzylpiperidin-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(5-acetarrddo-2-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(3,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ 2-[3-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-( 1 H-imidazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1R)- 1 -(3-cyanophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4-cyanophenyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(4-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 , 3-dihydro-2H-iso indole-2- carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [2-(pyridin-2-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyanomethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclohexylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimethylamino)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(phenylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [2-(diethylarrdno)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-aminophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1, 3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -arnino-4-methyl- 1 -oxopentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(3-chlorobenzyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-6-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-hydroxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(5-fluoropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tert-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)- 1 -benzylpyrrolidin-3-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(cyclopropylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(methylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(dimethylamino)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pentan-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentan-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(cyclobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [ 1 -(4-fluorophenyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l -phenyl- lH-pyrazol-4-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 2-[4-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(sec-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(2R)- 1 -hydroxy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -hydroxybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(prop-2-yn-l-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole -2-carboxamide;
5,6-dimethoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide; N-(4- { [3-(4-chlorophenoxy)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethoxy)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-phenyl- 1 ,3-thiazol-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
methyl 2- { [4-(propylcarbamoyl)phenyl] carbamoyl } isoindoline-5-carboxylate;
2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid;
5-amino-N- [4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; 5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-(aminomethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(2-hydroxy-2-methylpropanoyl)amino] -N- [4-(propylcarbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(N,N-dimethylglycyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-[(methylsulfonyl)amino] -N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
5-fluoro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(3R)-tetrahydrofuran-3-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(5-chloropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-hydroxy-4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-oxopyrrolidin- 1 -yl)benzyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(lS,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(l-hydroxycyclopropyl)methyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl] -5-vinyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- d]pyrimidine-6-carboxamide;
N-(4-{ [(3-phenylpropyl)amino]carbonyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- d]pyrimidine-6-carboxamide; 5-fluoro-N-[4-({ [(2S)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2R)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [( 1 S) -2-hydroxy- 1 -phenylethyl] amino } carbonyl)phenyl] -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-3-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-4-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N5-(2-methoxyethyl)-N2-{4-[(propylamino)carbonyl]phenyl}-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4 - { [(tetrahydrofuran-3 -ylmethyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
5-( 1 ,2-dihydroxyethyl)-N- { 4- [(propylamino)carbonyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [6-(benzoylamino)hexyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[(benzoylamino)methyl]benzyl}carbamoyl)phenyl]-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N5-[2-(dimethylamino)ethyl]-N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2,5-dicarboxamide; 5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(isobutoxycarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-phenylethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-(methylthio)butan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2S,3S)-1 -hydroxy-3-methylpentan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S,3R)-1, 3-dihydroxybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xyhexan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-1 -hydro xypentan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S,2S)-2-hydroxycyclopentyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(lS,2R) -2-hydroxycyclopentyl] carb amoyl } phenyl) -1,3 -dihydro -2H-isoindole-
2-carboxamide;
N-(4- { [(2S)- 1 -cyclohexyl-3-hydroxypropan-2-yl] carbamoyl jphenyl)- 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ (2R)- 1 -hydroxy-3-[(4-methylbenzyl)thio]propan-2-yl }carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(IS)- 1 -(4-tert-butylphenyl)-2-hydroxyethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide; 5-methoxy-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-memylpentan-2-yl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-(hydroxymethyl)-N- { 4-[(3-methylbutyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyljphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2-carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [3-(dimethylamino)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-methoxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ [(4S)-2,2-dimethyl-l,3-dioxolan-4-yl]methyljcarbamoyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide; N-[4-({ [(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}carbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2R)-butan-2-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[(cyclopentylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- { 4-[(l ,3-thiazol-5-ylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1R) -3 -hydroxy- 1 -phenylpropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(4-methylphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(l ,3-dihydroxypropan-2-yl)carbamoyl]phenylj - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2R)-l-hydroxy-3-methylbutan-2-yl]carbamoyljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2-(4-methylpiperazin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyljcarbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(4-hydroxybutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(3-furylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H-isoindole-2- carboxamide; 5-cyano-N- {4-[(tetrahydro furan-2-ylmemyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-tetrahydrofuran-2-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N- {4-[(tetrahydro furan-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2S)-1 -hydro xybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2,3-dihydroxypropyl)carbamoyl]phenylj - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(pyridin-2-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(l -hydroxy-4-methylpentan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide; N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-fluoro-N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl] methyl } carbamoyl)phenyl] - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -( { [ 1 -(morpholin-4 -yl)cyclopentyl] methyl } carbamoyl)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-fluoro-N-(4-{ [l-(l,3-thiazol-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4,4-difluorocyclohexyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- lH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5-fluoro- l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-D- phenylalanin amide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl}phenyl)-5- fluoro-l,3-dihydro-2H-isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl} -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(5-methyl-lH-pyrazol-l-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-chloro-lH-pyrazol-l-yl)ethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-5,7- dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-{4-[(2-carbamoylbenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 ,7-dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
Nalpha-{4-[(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-ylcarbonyl)amino]benzoyl}-L- phenylalanin amide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl }phenyl)-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(4,5,6,7-tetrahydro-lH-indazol-5-ylcarbamoyl)phenyl]-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3-methyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide; N-(4- { [(2R)- 1 -cyanobutan-2-yl]carbamoyl}phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrazol-3-yl)methyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(l -methoxybutan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl} -5-fluoro- l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(3-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(pyridin-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropyle thy 1] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(l-methylcyclopropyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N- { 4- [(thiophen-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(4-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(2S)- 1 -methoxypropan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrrol-2-yl)methyl]carbamoyl jphenyl)- 1,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyljphenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -amino- 1 -oxobutan-2-yl] carbamoyl }phenyl)-5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(l -methoxypropan-2-yl)carbamoyl]phenylj -l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl]-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4-{ [(2S)-2-methylbutyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5-fluoro-1 -dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -cyanoethyl)carbamoyl]phenyl } -5-fluoro- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(5-methyl-l,2-oxazol-3-yl)methyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-memoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(3-memyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(l-memyl-lH-pyrazol-3-yl)memyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [4-(dimemylarrdno)butyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(l,3-thiazol-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -methoxybutan-2-yl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-{4-[(4-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(2-ethoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{ 4-[( 1 -cyanocyclopropyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [(4-methyl- 1 ,3-thiazol-2-yl)methyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-{4-[(2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(lR)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(thiophen-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [(1 S)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide; N-(4-{ [(1 -methyl- lH-pyrrol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{ 4-[( 1 -cyanoethyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide; N- { 4- [(4,4-difluorocyclohexyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({2-[(dimethylamino)methyl]benzyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,3-oxazol-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(3,5 -dimethyl- IH-pyrazol- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [ 1 -( 1 ,3 -thiazol-2-yl)ethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(2,2-difluoroethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-4-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -L- phenylalanin amide;
N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)-3,3-dimethyl- 1 -(methylamino)- 1 -oxobutan-2-yl]carbamoyl jphenyl)- 1 ,3 dihydro-2H-isoindole-2-carboxamide;
N-[4-(thiophen-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(5-methyl- IH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3-methyl- IH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl } - 1 ,3-dmydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-3-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(acetylamino)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -methoxybutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pyrirnidin-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-( 1 H-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-methylbutyl] carbamoyl jphenyl)- 1, 3-dihydro-2H-iso indole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; and pharmaceutically acceptable salts thereof.
Embodiments of Formula (Vic)
In another aspect, the present invention provides compounds of Formula (Vic)
Figure imgf000557_0001
(Vic);
and pharmaceutically acceptable salts thereof; wherein R1 and R5 are as described herein for Formula (Ic); and n is 0 or 1.
In one embodiment of formula (Vic),
n is 0 or 1 ;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2, NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2, NHC(0)R , NR1UC(0)R , NHS02R , NHC(0)OR , S02NH2, S02NHR1U, S02N(R1U)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R , C(0)NR13S02R , S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl, wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl.
In another embodiment of Formula (Vic), n is 0. In another embodiment of Formula (Vic), n is 1. In another embodiment of Formula (Vic), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (Vic), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vic), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vic), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vic), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vic), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vic), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vic), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (Vic), R1 is C(0)NH2. In another embodiment of Formula (Vic), R1 is F. In another embodiment of Formula (Vic), R1 is CI. In another embodiment of Formula (Vic), R1 is Br. In another embodiment of Formula (Vic), R1 is CN. In another embodiment of Formula (Vic), R^s NH2. In another embodiment of Formula (Vic), R1 is N02. In another embodiment of Formula (Vic), R1 is CF3. In another embodiment of Formula (Vic), R1 is C(0)OH. In another embodiment of Formula (Vic), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (Vic), which include
N-{4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -( { [( 1 S) -2-hydroxy- 1 -phenylethyl] amino } carbonyl)phenyl] -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(azetidin- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [3-(dimethylamino)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4-{ [4-(dimethylamino)butyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-(4-{ [(l-methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl] methyl } carbamoyl)phenyl] - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -( { [ 1 -(morpholin-4 -yl)cyclopentyl] methyl } carbamoyl)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,6-diazaspiro[3.5]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Embodiments of Formula (VIIc)
Figure imgf000565_0001
(VIIc); and pharmaceutically acceptable salts thereof; wherein X1, X2, X3, and R13 are as described herein for Formula (Ic), and indicates a single or a double bond.
In one embodiment of formula (VIIc),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
1 is N; X2 is CR1; and X3 is N;
Figure imgf000566_0001
a single or double bond;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I; R , at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R6, andR10 are optionally substituted with one, two, three, four, five, or six independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl, wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In one embodiment of Formula (VIIc), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula
(VIIc), X1, X2, and X3 are CH. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (VIIc), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (VIIc),
X2 and X3 are CH; and X1 is N. In another embodiment of Formula (VIIc), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (VIIc), X1 is CR1; X2 is N; and X3 is CH.
In another embodiment of Formula (VIIc), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (VIIc), X1 is N; X2 is CR1; and X3 is N. In one embodiment of Formula (VIIc), is a single bond. In another embodiment of Formula (VIIc), is a double bond.
In another embodiment of Formula (VIIc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), R1 is C(0)NH2 In another embodiment of Formula (VIIc), R1 is F. In another embodiment of Formula (VIIc), R1 is CI. In another embodiment of Formula (VIIc), R1 is Br. In another embodiment of Formula (VIIc), R1 is CN. In another embodiment of Formula (VIIc), R^s NH2. In another embodiment of Formula (VIIc), R1 is N02. In another embodiment of Formula (VIIc), R1 is CF3. In another embodiment of Formula (VIIc), R1 is C(0)OH. In another embodiment of Formula (VIIc), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2,
NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR^ R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR^ R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R s NH2. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (VIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl;
wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR^ R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR^ R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (VIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R^s NH2. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (VIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
Still another embodiment pertains to compounds having Formula (VIIc), which include
tert-butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6- dihydropyridine- 1 (2H)-carboxylate;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperidine- 1 - carboxylate;
N-[4-(l-butyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxarnide;
N-[4-(l -isobutyrylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(4-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(5-oxo-D-prolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -propionyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [ 1 -(2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(ethoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[l-(2-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(3-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(4-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(4-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(4-chlorobenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[3-(dimethylamino)benzoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[4-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(3-thienylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(lH-pyrrol-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2,5 -dimethyl- lH-pyrrol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,3-thiazol-4-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(lH-pyrazol-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(3,5 -dimethyl- 1 ,2-oxazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-isonicotinoyl- 1,2,3, 6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide; N-{ 4-[l -(pyridazin-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrimidin-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[3-(piperidin- 1 -yl)propanoyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l-isobutyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [(2-methoxyethoxy)acetyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(2-hydro y-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ l-[(2R)-tetr ahydrofuran-2-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ 1-[(1 -methylpiperidin-4-yl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin -4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
5-cyano-N-{4-[l-(2-methylpropanoyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N- { 4- [ 1 -(N,N-dimethylglycyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3-methylbutanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [ 1 -(cyclopentylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-2-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(pyrrolidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- {4-[l-(tetrahydrofuran-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl }- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yl}phenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(2-methyl- 1 ,3-oxazol-4-yl)carbonyl]- 1 ,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(furan-3-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-3-(furan-2-yl)prop-2-enoyl] -1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,3-oxazol-5-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3,3,3-trifluoropropanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,5 -dimethyl- 1 H-pyrazol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methoxycyclohexyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,3-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2,2-difluorocyclopropyl)carbonyl] -1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(lH-pyrazol-5-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tert-butoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-l,2,4-triazol-l-yl)propanoyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-ethoxypropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-hydroxy-3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-pyrrol- l-yl)propanoyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylcyclopropyl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2-methylpropoxy)acetyl] -1,2, 3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l-(l-memylprolyl)-l,2 ,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -hydroxycyclopropyl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l - { [1 -(methoxymethyl)cyclopropyl]carbonyl } - 1 ,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(methylsulfonyl)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -acetyl- 1 ,2, 3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4- [1 -(eye loprop ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-4-methylpent-2-enoyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-methoxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopent- 1 -en- 1 -ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 - dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(thiophen-3-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-propanoyl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [ 1 -(2,2-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrrol-2-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,2-dimethylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(4-methylhexanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-dimethylcyclopropyl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-5-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclobutylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(piperidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[2-(pyrrolidin- 1 -yl)propanoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Embodiments of Formula (VIIIc)
One embodiment of this invention, therefore, pertains to compounds or
pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT, the compounds havin Formula (VIIIc)
Figure imgf000581_0001
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2,
NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; R , at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R6, R8, R10, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I; wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy;
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N. In one embodiment of Formula (VIIIc), X1, X2, and X3 are CH; or X1 and X3 are CH; and X2 is N; or X1 and X3 are CH; and X2 is CR1; or X2 and X3 are CH; and X1 is CR1; or X1 is CH; and X2 and X3 are CR1; or X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or X1 is CH; X2 is N; and X3 is CR1; or X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or X1 is N; X2 is CR1; and X3 is N. In another embodiment of Formula (VIIIc), X1, X2, and X3 are CH. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is N. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1. In another embodiment of Formula (VIIIc), X2 is CH; and X1 and X3 are N. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is N. In another embodiment of Formula (VIIIc), X1 is CH; X2 is N; and X3 is CR1. In another embodiment of Formula (VIIIc), X1 is CR1; X2 is N; and X3 is CH. In another embodiment of Formula (VIIIc), X1 is N; X2 is CR1; and X3 is CH. In another embodiment of Formula (VIIIc), X1 is N; X2 is CR1; and X3 is N.
In another embodiment of Formula (VIIIc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIIc), R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), R1 is OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), R1 is C(0)NH2 In another embodiment of Formula (VIIIc), R1 is F. In another embodiment of Formula (VIIIc), R1 is CI. In another embodiment of Formula (VIIIc), R1 is Br. In another embodiment of Formula (VIIIc), R1 is CN. In another embodiment of Formula (VIIIc), R^s NH2. In another embodiment of Formula (VIIIc), R1 is N02. In another embodiment of Formula (VIIIc), R1 is CF3. In another embodiment of Formula (VIIIc), R1 is C(0)OH. In another embodiment of Formula (VIIIc), R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl.
In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is OR3;
wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is F. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CI. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is Br. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CN. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R^s NH2. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is N02. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is CF3. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; and R1 is C(0)OH. In another embodiment of Formula (VIIIc), X1 and X3 are CH; and X2 is CR1; R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (VIIIc), X2 and X3 are CHj and X s CR^ and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; R1 is OR3;
wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)NH2. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is F. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CI. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is Br. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CN. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R^s NH2. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is N02. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is CF3. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)OH. In another embodiment of Formula (VIIIc), X2 and X3 are CH; and X1 is CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is R3, OR3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; R1 is R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; R1 is OR3;
wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)OR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; R1 is C(0)NHR3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; R1 is NHC(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; R1 is NHS02R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; wherein R6 is alkyl or heterocyclyl. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)NH2. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is F. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CI. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is Br. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CN. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and RHs NH2. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is N02. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is CF3. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)OH. In another embodiment of Formula (VIIIc), X1 is CH; and X2 and X3 are CR1; and R1 is C(0)R3; wherein R3 is alkyl, alkenyl, or heterocyclyl; wherein each alkyl is optionally substituted with one or more independently selected R6, OR6, NH2, NHC(0)R6, N(R6)2, or OH; and R6 is alkyl or heterocyclyl.
In one embodiment of Formula (VIIIc),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or X2 and X3 are CH; and X1 is N; or
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R3, at each occurrence, is independently selected alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one, two, three or four independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, OH, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl or heterocyclyl; wherein each R6 alkyl is optionally substituted with one, two, three or four independently selected F, CI, Br or I;
R8, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R8 alkyl is optionally substituted with one, two, three or four independently selected R12, OR12OH, CF3, F, CI, Br or I;
R12, at each occurrence, is independently selected alkyl, heterocyclyl, or cycloalkyl; wherein each R12 alkyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R6, R8, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)NHR13, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, S02R14, NH2, NHR14, N(R14)2, NHC(0)R14, NHC(0)OR14, OH, CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, OH, CN, CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, OH, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
In another embodiment of Formula (VIIIc),
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
R1 is R3, OR3, C(0)R3, C(0)OR3, C(0)NH2, C(0)NHR3, NHC(0)R3, NHS02R3, F, CI, Br, I, CN, NH2, N02, CF3, or C(0)OH;
R3, at each occurrence, is independently selected alkyl, alkenyl, or heterocyclyl; wherein each R3 alkyl is optionally substituted with one, two, three or four independently selected R6, OR6, NH2, N(R6)2, NHC(0)R6, or OH;
R6, at each occurrence, is independently selected alkyl or heterocyclyl;
R8, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R8 alkyl is optionally substituted with one, two, three or four independently selected R12, OR12OH, or CF3;
R12, at each occurrence, is independently selected alkyl, heterocyclyl, or cycloalkyl; wherein each R12 alkyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R6, R8, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, S02R13, C(0)R13, CO(0)R13, NH2, N(R13)2, NHC(0)R13, NHC(0)OR13, C(0)NH2, C(0)NHR13, C(0)N(R13)2, OH, CN, CF3, OCF3, SCF3, F, or CI;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl and alkynyl is optionally substituted with one, two, three or four independently selected R , OR , S02R , NH2, NHR14, N(R14)2, NHC(0)R14, NHC(0)OR14, OH, or CF3; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, S02R15, C(0)R15, N(R15)2, NHC(0)R15, CN, OH, CF3, F, or CI;
R14, at each occurrence, is independently selected alkyl, aryl, heterocyclyl, or cycloalkyl; wherein each R14 alkyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, or OH; wherein each R14 aryl, heterocyclyl, and cycloalkyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, or CI;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four independently selected alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
Still another embodiment pertains to compounds having Formula (VIIIc), which include
N- [4-( 1 -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-5-cyano-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [ 1 -(pyridin-2-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-chlorobenzoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl } butyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l -(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]butyl} -l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l -(cyclohexylcarbonyl)piperidin-4-yl]butyl}-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l -(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l -[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}butyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l -[(2-methoxyethoxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]butylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l -[(propan-2-yloxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l -(cyclopropylacetyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l -(4,4,4-trifluorobutanoyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
Pharmaceutical Compositions, Combination Therapies, Methods of Treatment, and
Administration
Another embodiment comprises pharmaceutical compositions comprising a compound having Formula (I) and an excipient.
Still another embodiment comprises methods of treating cancer in a mammal comprising administering thereto a therapeutically acceptable amount of a compound having Formula (I).
Still another embodiment pertains to compositions for treating diseases during which
NAMPT is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I).
Still another embodiment pertains to compositions for treating diseases during which ROCK is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I). Still another embodiment pertains to methods of treating disease in a patient during which NAMPT is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).
Still another embodiment pertains to methods of treating disease in a patient during which ROCK is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).
Still another embodiment pertains to compositions for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I).
Still another embodiment pertains to compositions for treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal- cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I). Still another embodiment pertains to methods of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).
Still another embodiment pertains to methods of treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal- cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I).
Still another embodiment pertains to compositions for treating diseases during which NAMPT is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Still another embodiment pertains to compositions for treating diseases during which
ROCK is expressed, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Still another embodiment pertains to methods of treating disease in a patient during which NAMPT is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Still another embodiment pertains to methods of treating disease in a patient during which ROCK is expressed, said methods comprising administering to the patient a therapeutically effective amount of a compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Still another embodiment pertains to compositions for treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Still another embodiment pertains to compositions for treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal- cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis, said compositions comprising an excipient and a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Still another embodiment pertains to methods of treating inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said methods comprising administering to the patient a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Still another embodiment pertains to methods of treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal- cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis in a patient, said methods comprising administering to the patient a therapeutically effective amount of the compound having Formula (I) and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
Metabolites of compounds having Formula (I), produced by in vitro or in vivo metabolic processes, may also have utility for treating diseases associated with NAMPT.
Metabolites of compounds having Formula (I), produced by in vitro or in vivo metabolic processes, may also have utility for treating diseases associated with ROCK.
Certain precursor compounds which may be metabolized in vitro or in vivo to form compounds having Formula (I) may also have utility for treating diseases associated with NAMPT.
Certain precursor compounds which may be metabolized in vitro or in vivo to form compounds having Formula (I) may also have utility for treating diseases associated with ROCK.
Compounds having Formula (I) may exist as acid addition salts, basic addition salts or zwitterions. Salts of the compounds are prepared during isolation or following purification of the compounds. Acid addition salts of the compounds are those derived from the reaction of the compounds with an acid. For example, the acetate, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsufonate, digluconate, formate, fumarate, glycerophosphate, glutamate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate, maleate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate, propionate, succinate, tartrate, thiocyanate, trichloroacetic, trifluoroacetic, para-toluenesulfonate, and undecanoate salts of the compounds are contemplated as being embraced by this invention. Basic addition salts of the compounds are those derived from the reaction of the compounds with the hydroxide, carbonate or bicarbonate of cations such as lithium, sodium, potassium, calcium, and magnesium.
The compounds having Formula (I) may be administered, for example, bucally, ophthalmically, orally, osmotically, parenterally (intramuscularly, intraperitoneally intrasternally, intravenously, subcutaneously), rectally, topically, transdermally or vaginally.
Therapeutically effective amounts of compounds having Formula (I) depend on the recipient of the treatment, the disorder being treated and the severity thereof, the composition containing the compound, the time of administration, the route of administration, the duration of treatment, the compound potency, its rate of clearance and whether or not another drug is co-administered. The amount of a compound of this invention having Formula (I) used to make a composition to be administered daily to a patient in a single dose or in divided doses is from about 0.03 to about 200 mg kg body weight. Single dose compositions contain these amounts or a combination of submultiples thereof. Compounds having Formula (I) may be administered with or without an excipient. Excipients include, for example, encapsulating materials or additives such as absorption accelerators, antioxidants, binders, buffers, coating agents, coloring agents, diluents, disintegrating agents, emulsifiers, extenders, fillers, flavoring agents, humectants, lubricants, perfumes, preservatives, propellants, releasing agents, sterilizing agents, sweeteners, solubilizers, wetting agents and mixtures thereof.
Excipients for preparation of compositions comprising a compound having Formula (I) to be administered orally in solid dosage form include, for example, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate, 1,3-butylene glycol, carbomers, castor oil, cellulose, cellulose acetate, cocoa butter, corn starch, corn oil, cottonseed oil, cross-povidone, diglycerides, ethanol, ethyl cellulose, ethyl laureate, ethyl oleate, fatty acid esters, gelatin, germ oil, glucose, glycerol, groundnut oil, hydroxypropylmethyl cellulose, isopropanol, isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglycerides, olive oil, peanut oil, potassium phosphate salts, potato starch, povidone, propylene glycol, Ringer's solution, safflower oil, sesame oil, sodium
carboxymethyl cellulose, sodium phosphate salts, sodium lauryl sulfate, sodium sorbitol, soybean oil, stearic acids, stearyl fumarate, sucrose, surfactants, talc, tragacanth, tetrahydrofurfuryl alcohol, triglycerides, water, and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered ophthalmically or orally in liquid dosage forms include, for example,
1,3-butylene glycol, castor oil, corn oil, cottonseed oil, ethanol, fatty acid esters of sorbitan, germ oil, groundnut oil, glycerol, isopropanol, olive oil, polyethylene glycols, propylene glycol, sesame oil, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered osmotically include, for example, chlorofluorohydrocarbons, ethanol, water and mixtures thereof.
Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered parenterally include, for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, germ oil, groundnut oil, liposomes, oleic acid, olive oil, peanut oil, Ringer's solution, safflower oil, sesame oil, soybean oil, U.S. P. or isotonic sodium chloride solution, water and mixtures thereof. Excipients for preparation of compositions comprising a compound of this invention having Formula (I) to be administered rectally or vaginally include, for example, cocoa butter, polyethylene glycol, wax and mixtures thereof.
Compounds having Formula (I) are expected to be useful when used with alkylating agents, angiogenesis inhibitors, antibodies, antimetabolites, antimitotics, antiproliferatives, antivirals, aurora kinase inhibitors, apoptosis promoters (for example, Bcl-xL, Bcl-w and Bfl- 1) inhibitors, activators of death receptor pathway, Bcr-Abl kinase inhibitors, BiTE (Bi- Specific T cell Engager) antibodies, antibody drug conjugates, biologic response modifiers, cyclin-dependent kinase inhibitors, cell cycle inhibitors, cyclooxygenase-2 inhibitors, DVDs, leukemia viral oncogene homolog (ErbB2) receptor inhibitors, growth factor inhibitors, heat shock protein (HSP)-90 inhibitors, histone deacetylase (HDAC) inhibitors, hormonal therapies, immunologicals, inhibitors of inhibitors of apoptosis proteins (IAPs), intercalating antibiotics, kinase inhibitors, kinesin inhibitors, Jak2 inhibitors, mammalian target of rapamycin inhibitors, microRNA' s, mitogen-activated extracellular signal-regulated kinase inhibitors, multivalent binding proteins, non-steroidal anti-inflammatory drugs (NSAIDs), poly ADP (adenosine diphosphate)-ribose polymerase (PARP) inhibitors, platinum chemotherapeutics, polo-like kinase (Plk) inhibitors, phosphoinositide-3 kinase (PI3K) inhibitors, proteosome inhibitors, purine analogs, pyrimidine analogs, receptor tyrosine kinase inhibitors, retinoids/deltoids plant alkaloids, small inhibitory ribonucleic acids (siRNAs), topoisomerase inhibitors, ubiquitin ligase inhibitors, and the like, and in combination with one or more of these agents .
BiTE antibodies are bi-specific antibodies that direct T-cells to attack cancer cells by simultaneously binding the two cells. The T-cell then attacks the target cancer cell.
Examples of BiTE antibodies include adecatumumab (Micromet MT201), blinatumomab (Micro met MT103) and the like. Without being limited by theory, one of the mechanisms by which T-cells elicit apoptosis of the target cancer cell is by exocytosis of cytolytic granule components, which include perforin and granzyme B. In this regard, Bcl-2 has been shown to attenuate the induction of apoptosis by both perforin and granzyme B. These data suggest that inhibition of Bcl-2 could enhance the cytotoxic effects elicited by T-cells when targeted to cancer cells (V.R. Sutton, D.L. Vaux and J. A. Trapani, J. of Immunology 1997, 158 (12), 5783).
SiRNAs are molecules having endogenous RNA bases or chemically modified nucleotides. The modifications do not abolish cellular activity, but rather impart increased stability and/or increased cellular potency. Examples of chemical modifications include phosphorothioate groups, 2'-deoxynucleotide, 2'-OCH3-containing ribonucleotides, 2'-F- ribonucleotides, 2'-methoxyethyl ribonucleotides, combinations thereof and the like. The siRNA can have varying lengths (e.g., 10-200 bps) and structures (e.g., hairpins, single/double strands, bulges, nicks/gaps, mismatches) and are processed in cells to provide active gene silencing. A double-stranded siRNA (dsRNA) can have the same number of nucleotides on each strand (blunt ends) or asymmetric ends (overhangs). The overhang of 1 -2 nucleotides can be present on the sense and/or the antisense strand, as well as present on the 5'- and/ or the 3'-ends of a given strand.
Multivalent binding proteins are binding proteins comprising two or more antigen binding sites. Multivalent binding proteins are engineered to have the three or more antigen binding sites and are generally not naturally occurring antibodies. The term "multispecific binding protein" means a binding protein capable of binding two or more related or unrelated targets. Dual variable domain (DVD) binding proteins are tetravalent or multivalent binding proteins binding proteins comprising two or more antigen binding sites. Such DVDs may be monospecific (i.e., capable of binding one antigen) or multispecific (i.e., capable of binding two or more antigens). DVD binding proteins comprising two heavy chain DVD polypeptides and two light chain DVD polypeptides are referred to as DVD Ig's. Each half of a DVD Ig comprises a heavy chain DVD polypeptide, a light chain DVD polypeptide, and two antigen binding sites. Each binding site comprises a heavy chain variable domain and a light chain variable domain with a total of 6 CDRs involved in antigen binding per antigen binding site.
Alkylating agents include altretamine, AMD-473, AP-5280, apaziquone, bendamustine, brostallicin, busulfan, carboquone, carmustine (BCNU), chlorambucil, CLORETAZINE® (laromustine, VNP 40101M), cyclophosphamide, decarbazine, estramustine, fotemustine, glufosfamide, ifosfamide, KW-2170, lomustine (CCNU), mafosfamide, melphalan, mitobronitol, mitolactol, nimustine, nitrogen mustard N-oxide, ranimustine, temozolomide, thiotepa, TREANDA® (bendamustine), treosulfan, trofosfamide and the like.
Angiogenesis inhibitors include endothelial-specific receptor tyrosine kinase (Tie-2) inhibitors, epidermal growth factor receptor (EGFR) inhibitors, insulin growth factor-2 receptor (IGFR-2) inhibitors, matrix metalloproteinase-2 (MMP-2) inhibitors, matrix metalloproteinase-9 (MMP-9) inhibitors, platelet-derived growth factor receptor (PDGFR) inhibitors, thrombospondin analogs, vascular endothelial growth factor receptor tyrosine kinase (VEGFR) inhibitors and the like.
Antimetabolites include ALIMTA® (pemetrexed disodium, LY231514, MTA), 5-azacitidine, XELODA® (capecitabine), carmofur, LEUSTAT® (cladribine), clofarabine, cytarabine, cytarabine ocfosfate, cytosine arabinoside, decitabine, deferoxamine, doxifluridine, eflornithine, EICAR (5-ethynyl-l-P -D-ribofuranosylimidazole-4- carboxamide), enocitabine, ethnylcytidine, fludarabine, 5-fluorouracil alone or in combination with leucovorin, GEMZAR® (gemcitabine), hydroxyurea, ALKERAN® (melphalan), mercaptopurine, 6-mercaptopurine riboside, methotrexate, mycophenolic acid, nelarabine, nolatrexed, ocfosfate, pelitrexol, pentostatin, raltitrexed, Ribavirin, triapine, trimetrexate, S-1, tiazofurin, tegafur, TS-1, vidarabine, UFT and the like.
Antivirals include ritonavir, hydroxychloroquine and the like.
Aurora kinase inhibitors include ABT-348, AZD-1152, MLN-8054, VX-680, Aurora A-specific kinase inhibitors, Aurora B-specific kinase inhibitors and pan-Aurora kinase inhibitors and the like. Bcl-2 protein inhibitors include AT-101 ((-)gossypol), GENASENSE® (G3139 or oblimersen (Bcl-2-targeting antisense oligonucleotide)), IPI-194, IPI-565, N-(4-(4-((4'- chloro(l , 1 '-biphenyl)-2-yl)methyl)piperazin- 1 -yl)benzoyl)-4-(((lR)-3-(dimethylamino)- 1 - ((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide) (ABT-737), N-(4-(4-((2- (4-chlorophenyl)-5,5 -dimethyl- 1 -cyclohex-1 -en- 1 -yl)methyl)piperazin- 1 -yl)benzoyl)-4- (((lR)-3-(morpholin-4-yl)-l-((phenylsulfanyl)methyl)propyl)amino)-3- ((trifluoromethyl)sulfonyl)benzenesulfonamide (ABT-263), GX-070 (obatoclax) and the like.
Bcr-Abl kinase inhibitors include DASATINIB® (BMS-354825), GLEEVEC® (imatinib) and the like.
CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584, flavopyridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib (CYC-202,
R-roscovitine), ZK-304709 and the like.
COX-2 inhibitors include ABT-963, ARCOXIA® (etoricoxib), BEXTRA®
(valdecoxib), BMS347070, CELEBREX® (celecoxib), COX-189 (lumiracoxib), CT-3, DERAMAXX® (deracoxib), JTE-522, 4-methyl-2-(3,4-dimethylphenyl)-l-(4- sulfamoylphenyl-lH-pyrrole), MK-663 (etoricoxib), NS-398, parecoxib, RS-57067,
SC-58125, SD-8381, SVT-2016, S-2474, T-614, VIOXX® (rofecoxib) and the like.
EGFR inhibitors include ABX-EGF, anti-EGFR immunoliposomes, EGF-vaccine,
EMD-7200, ERBITUX® (cetuximab), HR3, IgA antibodies, IRESSA® (gefitinib),
TARCEVA® (erlotinib or OSI-774), TP-38, EGFR fusion protein, TYKERB® (lapatinib) and the like.
ErbB2 receptor inhibitors include CP-724-714, CI-1033 (canertinib), HERCEPTIN® (trastuzumab), TYKERB® (lapatinib), OMNITARG® (2C4, petuzumab), TAK-165, GW-572016 (ionafarnib), GW-282974, EKB-569, PI-166, dHER2 (HER2 vaccine), APC-8024 (HER-2 vaccine), anti-HER/2neu bispecific antibody, B7.her2IgG3, AS HER2 trifunctional bispecfic antibodies, mAB AR-209, mAB 2B-1 and the like.
Histone deacetylase inhibitors include depsipeptide, LAQ-824, MS-275, trapoxin, suberoylanilide hydroxamic acid (SAHA), TSA, valproic acid and the like.
HSP-90 inhibitors include 17-AAG-nab, 17-AAG, CNF-101, CNF- 1010, CNF-2024, 17-DMAG, geldanamycin, IPI-504, KOS-953, MYCOGRAB® (human recombinant antibody to HSP-90), NCS-683664, PU24FC1, PU-3, radicicol, SNX-2112, STA-9090 VER49009 and the like.
Inhibitors of inhibitors of apoptosis proteins include HGS1029, GDC -0145, GDC- 0152, LCL-161, LBW-242 and the like.
Antibody drug conjugates include anti-CD22-MC-MMAF, anti-CD22-MC-MMAE, anti-CD22-MCC-DMl, CR-011-vcMMAE, PSMA-ADC, MEDI-547, SGN-19Am SGN-35, SGN-75 and the like Activators of death receptor pathway include TRAIL, antibodies or other agents that target TRAIL or death receptors (e.g., DR4 and DR5) such as Apomab, conatumumab, ETR2- ST01, GDC0145 (lexatumumab), HGS-1029, LBY-135, PRO-1762 and trastuzumab.
Kinesin inhibitors include Eg5 inhibitors such as AZD4877, ARRY-520; CENPE inhibitors such as GSK923295A and the like.
JAK-2 inhibitors include CEP-701 (lesaurtinib), XL019 and INCB018424 and the like.
MEK inhibitors include ARRY-142886, ARRY-438162 PD-325901, PD-98059 and the like.
mTOR inhibitors include AP-23573, CCI-779, everolimus, RAD-001, rapamycin, temsirolimus, ATP-competitive TORC1/TORC2 inhibitors, including PI-103, PP242, PP30, Torin 1 and the like.
Non-steroidal anti-inflammatory drugs include AMIGESIC® (salsalate), DOLOBID® (diflunisal), MOTRIN® (ibuprofen), ORUDIS® (ketoprofen), RELAFEN® (nabumetone), FELDENE® (piroxicam), ibuprofen cream, ALEVE® (naproxen) and NAPROSYN®
(naproxen), VOLTAREN® (diclofenac), INDOCIN® (indomethacin), CLINORIL® (sulindac), TOLECTIN® (tolmetin), LODINE® (etodolac), TORADOL® (ketorolac), DAYPRO® (oxaprozin) and the like.
PDGFR inhibitors include C-451, CP-673, CP-868596 and the like.
Platinum chemotherapeutics include cisplatin, ELOXATIN® (oxaliplatin) eptaplatin, lobaplatin, nedaplatin, PARAPLATIN® (carboplatin), satraplatin, picoplatin and the like.
Polo-like kinase inhibitors include BI-2536 and the like.
Phosphoinositide-3 kinase (PI3K) inhibitors include wortmannin, LY294002, XL- 147, CAL-120, ONC-21, AEZS-127, ETP-45658, PX-866, GDC -0941, BGT226, BEZ235, XL765 and the like.
Thrombospondin analogs include ABT-510, ABT-567, ABT-898, TSP-1 and the like.
VEGFR inhibitors include AVASTIN® (bevacizumab), ABT-869, AEE-788, ANGIOZYME™ (a ribozyme that inhibits angiogenesis (Ribozyme Pharmaceuticals (Boulder, CO.) and Chiron, (Emeryville, CA)) , axitinib (AG-13736), AZD-2171,
CP-547,632, IM-862, MACUGEN (pegaptamib), NEXAVAR® (sorafenib, BAY43-9006), pazopanib (GW-786034), vatalanib (PTK-787, ZK-222584), SUTENT® (sunitinib, SU- 11248), VEGF trap, ZACTIMA™ (vandetanib, ZD-6474) and the like.
Antibiotics include intercalating antibiotics aclarubicin, actinomycin D, amrubicin, annamycin, adriamycin, BLENOXANE® (bleomycin), daunorubicin, CAELYX® or
MYOCET® (liposomal doxorubicin), elsamitrucin, epirbucin, glarbuicin, ZAVEDOS® (idarubicin), mitomycin C, nemorubicin, neocarzinostatin, peplomycin, pirarubicin, rebeccamycin, stimalamer, streptozocin, VALSTAR® (valrubicin), zinostatin and the like.
Topoisomerase inhibitors include aclarubicin, 9-aminocamptothecin, amonafide, amsacrine, becatecarin, belotecan, BN-80915, CAMPTOSAR® (irinotecan hydrochloride), camptothecin, CARDIOXANE® (dexrazoxine), diflomotecan, edotecarin, ELLENCE® or
PHARMORUBICIN® (epirubicin), etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan, mitoxantrone, orathecin, pirarbucin, pixantrone, rubitecan, sobuzoxane, SN-38, tafluposide, topotecan and the like.
Antibodies include AVASTIN® (bevacizumab), CD40-specific antibodies, chTNT- 1 B, denosumab, ERBITUX® (cetuximab), HUMAX-CD4® (zanolimumab), IGFlR-specific antibodies, lintuzumab, PANOREX® (edrecolomab), RENCAREX® (WX G250),
RITUXAN® (rituximab), ticilimumab, trastuzimab, CD20 antibodies types I and II and the like.
Hormonal therapies include ARIMIDEX® (anastrozole), AROMASIN® (exemestane), arzoxifene, CASODEX® (bicalutamide), CETROTIDE® (cetrorelix), degarelix, deslorelin, DESOPAN® (trilostane), dexamethasone, DROGENIL® (flutamide), EVISTA® (raloxifene), AFEMA™ (fadrozole), FARESTON® (toremifene), FASLODEX® (fulvestrant), FEMARA® (letrozole), formestane, glucocorticoids, HECTOROL® (doxercalciferol), RENAGEL® (sevelamer carbonate), lasofoxifene, leuprolide acetate, MEGACE® (megesterol),
MIFEPREX® (mifepristone), NILANDRON™ (nilutamide), NOLVADEX® (tamoxifen citrate), PLENAXIS™ (abarelix), prednisone, PROPECIA® (finasteride), rilostane,
SUPREFACT® (buserelin), TRELSTAR® (luteinizing hormone releasing hormone (LHRH)), VANTAS® (Histrelin implant), VETORYL® (trilostane or modrastane), ZOLADEX® (fosrelin, goserelin) and the like.
Deltoids and retinoids include seocalcitol (EB1089, CB1093), lexacalcitrol
(KH1060), fenretinide, PANRETIN® (aliretinoin), ATRAGEN® (liposomal tretinoin), TARGRETIN® (bexarotene), LGD-1550 and the like.
PARP inhibitors include ABT-888 (veliparib), olaparib, KU-59436, AZD-2281, AG- 014699, BSI-201, BGP-15, INO-1001, ONO-2231 and the like.
Plant alkaloids include, but are not limited to, vincristine, vinblastine, vindesine, vinorelbine and the like.
Proteasome inhibitors include VELCADE® (bortezomib), MG132, NPI-0052, PR- 171 and the like.
Examples of immunologicals include interferons and other immune-enhancing agents. Interferons include interferon alpha, interferon alpha-2a, interferon alpha-2b, interferon beta, interferon gamma- la, ACTIMMUNE® (interferon gamma- lb) or interferon gamma-nl, combinations thereof and the like. Other agents include ALFAFERONE® ,(IFN- a), BAM-002 (oxidized glutathione), BEROMUN® (tasonermin), BEXXAR® (tositumomab), CAMPATH® (alemtuzumab), CTLA4 (cytotoxic lymphocyte antigen 4), decarbazine, denileukin, epratuzumab, GRANOCYTE® (lenograstim), lentinan, leukocyte alpha interferon, imiquimod, MDX-010 (anti-CTLA-4), melanoma vaccine, mitumomab, molgramostim, MYLOTARG™ (gemtuzumab ozogamicin), NEUPOGEN® (filgrastim), OncoVAC-CL, OVAREX® (oregovomab), pemtumomab (Y-muHMFGl), PROVENGE® (sipuleucel-T), sargaramostim, sizofilan, teceleukin, THERACYS® (Bacillus Calmette-Guerin), ubenimex, VIRULIZIN® (immunotherapeutic, Lorus Pharmaceuticals), Z-100 (Specific Substance of Maruyama (SSM)), WF-10 (Tetrachlorodecaoxide (TCDO)), PROLEUKIN® (aldesleukin), ZADAXIN® (thymalfasin), ZENAPAX® (daclizumab), ZEVALIN® (90Y-ibritumomab tiuxetan) and the like.
Biological response modifiers are agents that modify defense mechanisms of living organisms or biological responses, such as survival, growth or differentiation of tissue cells to direct them to have anti-tumor activity and include krestin, lentinan, sizofiran, picibanil PF- 3512676 (CpG-8954), ubenimex and the like.
Pyrimidine analogs include cytarabine (ara C or Arabinoside C), cytosine arabinoside, doxifluridine, FLUDARA® (fludarabine), 5-FU (5-fluorouracil), floxuridine, GEMZAR® (gemcitabine), TOMUDEX® (ratitrexed), TROXATYL™ (triacetyluridine troxacitabine) and the like.
Purine analogs include LANVIS® (thioguanine) and PURI-NETHOL®
(mercaptopurine) .
Antimitotic agents include batabulin, epothilone D (KOS-862), N-(2-((4- hydroxyphenyl)arnino)pyridin-3-yl)-4-methoxybenzenesulfonamide, ixabepilone (BMS 247550), paclitaxel, TAXOTERE® (docetaxel), PNU100940 (109881), patupilone, XRP-9881 (larotaxel), vinflunine, ZK-EPO (synthetic epothilone) and the like.
Ubiquitin ligase inhibitors include MDM2 inhibitors, such as nutlins, NEDD8 inhibitors such as MLN4924 and the like.
Compounds of this invention can also be used as radiosensitizers that enhance the efficacy of radiotherapy. Examples of radiotherapy include external beam radiotherapy, teletherapy, brachytherapy and sealed, unsealed source radiotherapy and the like.
Additionally, compounds having Formula (I) may be combined with other chemotherapeutic agents such as ABRAXANE™ (AB 1-007), ABT-100 (farnesyl transferase inhibitor), ADVEXIN® (Ad5CMV-p53 vaccine), ALTOCOR® or MEVACOR® (lovastatin), AMPLIGEN® (poly Lpoly C12U, a synthetic RNA), APTOSYN® (exisulind), AREDIA® (pamidronic acid), arglabin, L-asparaginase, atamestane (l-methyl-3,17-dione-androsta-l,4- diene), AVAGE® (tazarotene), AVE-8062 (combreastatin derivative) BEC2 (mitumomab), cachectin or cachexin (tumor necrosis factor), canvaxin (vaccine), CEAVAC® (cancer vaccine), CELEUK® (celmoleukin), CEPLENE® (histamine dihydrochloride), CERVARIX® (human papillomavirus vaccine), CHOP® (C: CYTOXAN® (cyclophosphamide); H:
ADRIAMYCIN® (hydroxydoxorubicin); O: Vincristine (ONCOVIN®); P: prednisone), CYPAT™ (cyproterone acetate), combrestatin A4P, DAB(389)EGF (catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor) or TransMiD-107R™ (diphtheria toxins), dacarbazine, dactinomycin, 5,6- dimethylxanthenone-4-acetic acid (DMXAA), eniluracil, EVIZON™ (squalamine lactate), DIMERICINE® (T4N5 liposome lotion), discodermolide, DX-8951f (exatecan mesylate), enzastaurin, EPO906 (epithilone B), GARDASIL® (quadrivalent human papillomavirus (Types 6, 11, 16, 18) recombinant vaccine), GASTRIMMUNE®, GENASENSE®, GMK
(ganglioside conjugate vaccine), GVAX® (prostate cancer vaccine), halofuginone, histerelin, hydroxycarbamide, ibandronic acid, IGN-101, IL-13-PE38, IL-13-PE38QQR (cintredekin besudotox), IL-13-pseudomonas exotoxin, interferon-a, interferon-γ, JUNOVAN™ or MEPACT™ (mifamurtide), lonafarnib, 5,10-methylenetetrahydrofolate, miltefosine (hexadecylphosphocholine), NEOVASTAT®(AE-941), NEUTREXIN® (trimetrexate glucuronate), NIPENT® (pentostatin), ONCONASE® (a ribonuclease enzyme),
ONCOPHAGE® (melanoma vaccine treatment), ONCOVAX® (IL-2 Vaccine),
ORATHECIN™ (rubitecan), OSIDEM® (antibody-based cell drug), OVAREX® MAb (murine monoclonal antibody), paclitaxel, PANDIMEX™ (aglycone saponins from ginseng comprising 20(S)protopanaxadiol (aPPD) and 20(S)protopanaxatriol (aPPT)), panitumumab, PANVAC®-VF (investigational cancer vaccine), pegaspargase, PEG Interferon A, phenoxodiol, procarbazine, rebimastat, REMOVAB® (catumaxomab), REVLIMID® (lenalidomide), RSR13 (efaproxiral), SOMATULINE® LA (lanreotide), SORIATANE® (acitretin), staurosporine (Streptomyces staurospores), talabostat (PT100), TARGRETIN® (bexarotene), TAXOPREXIN® (DHA-paclitaxel), TELCYTA® (canfosfamide, TLK286), temilifene, TEMODAR® (temozolomide), tesmilifene, thalidomide, THERATOPE® (STn- KLH), thymitaq (2-amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)quinazoline dihydrochloride), TNFERADE™ (adenovector: DNA carrier containing the gene for tumor necrosis factor-a), TRACLEER® or ZAVESCA® (bosentan), tretinoin (Retin-A), tetrandrine, TRISENOX® (arsenic trioxide), VIRULIZIN®, ukrain (derivative of alkaloids from the greater celandine plant), vitaxin (anti-alphavbeta3 antibody), XCYTRIN® (motexafin gadolinium), XINLAY™ (atrasentan), XYOTAX™ (paclitaxel poliglumex), YONDELIS® (trabectedin), ZD-6126, ZINECARD® (dexrazoxane), ZOMETA® (zolendronic acid), zorubicin and the like. Data
Determination of the utility of compounds having Formula (I) as binders to and inhibitors of NAMPT was performed using a Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) binding assay.
Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay of
NAMPT
The assay was carried out in 18 uL low volume plates (Owens Corning) in reaction buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1 % Glycerol) using 6.8 nM recombinant, human, C-terminally-His tagged NAMPT, 1 nM Tb- anti-His antibody (Invitrogen, Cat # PV5895), and 200 nM probe (Oregon Green 488- conjugated AP0866; A-1251667.0 (probe 1) or A- 1287128.0 (probe 2)). Plates were covered, and reactions were carried out for 2-3 hours. Plates were read with Envision (Laser Lantha low volume protocol) after 2 to 3 hours. Excitation was carried out at 337 nm, and the ratio of emission of Oregon Green (520 nm) to terbium (492 nm) was determined and used to calculate IC50 values of test compounds.
TABLE 1 shows the utility of compounds having Formula I to functionally inhibit NAMPT.
Table 1
Figure imgf000606_0001
0.0126, nd 806 nd, 0.286
0.0138, nd 807 nd, 0.0417
0.0141, nd 808 nd, 0.696
0.0145, nd 809 nd, 0.00207
0.0146, nd 810 nd, nd
0.0149, nd 811 nd, 0.00359
0.015, nd 812 nd, 0.00679
0.015, nd 813 nd, 0.0446
0.0151, nd 814 nd, 0.00713
0.0152, nd 815 nd, 0.00287
0.0157, nd 816 nd, 0.0243
0.0161, nd 817 nd, 0.00251
0.0164, nd 818 nd, 0.0128
0.0166, nd 819 nd, 0.00428
0.0171, nd 820 nd, 0.00631
0.0174, nd 821 nd, 0.012
0.0174, 0.0173 822 nd, 0.00207
0.0178, nd 823 nd, 0.00176
0.018, nd 824 nd, 0.0066
0.0181, nd 825 nd, 0.0107
0.0183, nd 826 nd, 0.00918
0.0185, nd 827 nd, 0.00311
0.0186, nd 828 nd, 0.00737
0.0186, nd 829 nd, 0.00359 nd, nd 830 nd, nd
0.0191, nd 831 nd, 0.00918
0.0197, nd 832 nd, 0.00888
0.0197, nd 833 nd, 0.0034
0.0201, nd 834 nd, 0.00358
0.0202, nd 835 nd, 0.00353
0.0203, nd 836 nd, 0.00454
0.021 l, nd 837 nd, 0.00367
0.0212, nd 838 nd, 0.00203
0.0229, 0.0154 839 nd, 0.0191
0.0224, nd 840 nd, 0.725
0.0225, nd 841 nd, 1.61
0.0231, nd 842 nd, 0.0746
0.0236, nd 843 nd, 0.704
0.0237, nd 844 nd, 2.62
0.0238, nd 845 nd, 5.64
0.024, nd 846 nd, 2.99
0.0241, nd 847 nd, 0.24
0.0247, nd 848 nd, 1.19
0.0248, nd 849 nd, 5.71
0.0248, nd 850 nd, 2.1
0.0256, nd 851 nd, 0.277
0.0258, nd 852 nd, 5.48
0.0267, nd 853 nd, 12.5
0.0273, nd 854 nd, 5.66
0.0274, nd 855 nd, 0.839
0.0278, nd 856 nd, 0.00913
0.0284, nd 857 nd, 0.061
0.0293, nd 858 nd, 0.0082 79 0.0295, nd 859 nd, 2.14
80 0.0299, nd 860 nd, 12.5
81 0.0301, nd 861 nd, 3.15
82 0.0301, nd 862 nd, 0.599
83 0.0306, nd 863 nd, 0.143
84 0.0308, nd 864 nd, 0.122
85 0.0313, nd 865 nd, 1.56
86 0.0319, nd 866 nd, 0.14
87 0.0326, nd 867 nd, 0.0593
88 0.033, nd 868 nd, 0.128
89 0.0334, nd 869 nd, 0.229
90 0.0335, nd 870 nd, 0.12
91 0.0342, nd 871 nd, 0.036
92 0.0346, nd 872 nd, 0.00746
93 0.0351, nd 873 nd, 0.00465
94 0.0354, nd 874 nd, 0.00231
95 nd, nd 875 nd, 0.00419
96 0.0365, nd 876 nd, 0.0022
97 0.037, nd 877 nd, 0.00882
98 0.0381, nd 878 nd, 0.0525
99 0.0382, nd 879 nd, 0.00298
100 nd, nd 880 nd, 0.0517
101 0.0393, nd 881 nd, 0.0463
102 0.0395, nd 882 nd, 0.0377
103 0.0395, nd 883 nd, 0.0156
104 0.0395, nd 884 nd, 0.0154
105 0.0397, nd 885 nd, 0.466
106 0.0263, nd 886 nd, 0.0246
107 0.0408, nd 887 nd, 0.826
108 0.0408, nd 888 nd, 0.0934
109 0.0412, nd 889 nd, 1.47
110 0.0422, nd 890 nd, 1.38
111 0.044, nd 891 nd, 1.72
112 0.0445, nd 892 nd, 1.84
113 0.0445, nd 893 nd, 0.154
114 0.0461, nd 894 nd, 0.00302
115 0.0465, nd 895 nd, 0.0261
116 0.0465, nd 896 nd, 0.444
117 0.0481, nd 897 nd, 0.969
118 0.0481, nd 898 nd, 0.288
119 0.0484, nd 899 nd, 0.19
120 0.049, nd 900 nd, 0.0437
121 0.0493, nd 901 nd, 0.0676
122 0.0511, nd 902 nd, 0.35
123 0.0515, nd 903 nd, 0.0491
124 0.0517, nd 904 nd, 0.0351
125 0.0518, nd 905 nd, 0.0383
126 0.0537, nd 906 nd, 0.0569
127 0.0539, nd 907 nd, 0.0711
128 0.0553, nd 908 nd, 0.0334
129 0.0567, nd 909 nd, 0.0019
130 0.0567, nd 910 nd, 0.00638
131 0.0573, nd 911 nd, 0.0133 132 0.0581, nd 912 nd, 0.00832
133 0.0582, nd 913 nd, 0.0074
134 0.0613, nd 914 nd, 0.00486
135 0.0615, nd 915 nd, 0.0188
136 0.0616, nd 916 nd, 0.0221
137 0.0629, nd 917 nd, 0.00207
138 0.0632, nd 918 nd, 0.0128
139 0.0638, nd 919 nd, 0.00708
140 0.0655, nd 920 nd, 0.548
141 0.0656, nd 921 nd, 0.0602
142 0.0664, nd 922 nd, 0.00567
143 0.0665, nd 923 nd, 0.00395
144 0.0666, nd 924 nd, 0.00277
145 0.0692, nd 925 nd, 0.00683
146 0.0694, nd 926 nd, 0.0508
147 0.0701, nd 927 nd, 0.0406
148 0.0702, nd 928 nd, 0.0725
149 0.0717, nd 929 nd, 0.21
150 0.0728, nd 930 nd, 0.146
151 0.0733, nd 931 nd, 0.0981
152 0.0759, nd 932 nd, 1.31
153 0.0799, nd 933 nd, 0.206
154 0.0813, nd 934 nd, 0.00168
155 0.0834, nd 935 nd, 0.00584
156 0.0836, nd 936 nd, 0.121
157 0.0846, nd 937 nd, 0.0398
158 0.0857, nd 938 nd, 0.0877
159 0.0858, nd 939 nd, 0.0105
160 0.0861, nd 940 nd, 0.0168
161 0.0876, nd 941 nd, 0.136
162 0.0882, nd 942 nd, 0.0238
163 0.0893, nd 943 nd, 0.0090
164 0.0907, nd 944 nd, 0.0328
165 0.0931, nd 945 nd, 0.0433
166 0.0999, nd 946 nd, 0.0172
167 0.101, nd 947 nd, 0.0459
168 0.105, nd 948 nd, 0.0192
169 0.108, nd 949 nd, 0.0309
170 0.108, nd 950 nd, 0.0198
171 0.11, nd 951 nd, 0.00968
172 0.111, nd 952 nd, 0.0128
173 0.115, nd 953 nd, 0.426
174 0.12, nd 954 nd, 0.341
175 0.12, nd 955 nd, 0.222
176 0.12, nd 956 nd, 0.346
177 0.123, nd 957 nd, 0.374
178 nd, nd 958 nd, 0.148
179 0.128, nd 959 nd, 0.307
180 0.131, nd 960 nd, 0.22
181 0.133, nd 961 nd, 0.161
182 0.136, nd 962 nd, 0.201
183 0.14, nd 963 nd, 0.198
184 0.141, nd 964 nd, 0.128 185 0.142, nd 965 nd, 0.17
186 0.145, nd 966 nd, 0.223
187 0.146, nd 967 nd, 0.0047
188 0.148, nd 968 nd, 0.00259
189 0.149, nd 969 nd, 0.0234
190 0.15, nd 970 nd, 0.0213
191 0.154, nd 971 nd, 0.0205
192 0.155, nd 972 nd, 0.00919
193 0.164, nd 973 nd, 0.0435
194 0.164, nd 974 nd, 0.034
195 0.172, nd 975 nd, 0.0115
196 0.176, nd 976 nd, 0.0225
197 0.178, nd 977 nd, 0.0214
198 0.179, nd 978 nd, 0.0236
199 0.179, nd 979 nd, 0.0365
200 0.186, nd 980 nd, 0.0173
201 0.189, nd 981 nd, 0.034
202 0.192, nd 982 nd, 0.0144
203 0.198, nd 983 nd, 0.0296
204 0.20, nd 984 nd, 0.0689
205 0.203, nd 985 nd, 0.00963
206 0.216, nd 986 nd, 0.0407
207 0.219, nd 987 nd, 0.111
208 0.223, nd 988 nd, nd
209 0.146, 0.258 989 nd, 0.0269
210 0.235, Nd 990 nd, 0.031
211 0.241, nd 991 nd, 0.0408
212 0.252, nd 992 nd, 0.0168
213 0.255, nd 993 nd, 0.00941
214 0.265, nd 994 nd, 0.00802
215 0.267, nd 995 nd, 0.0285
216 0.271, nd 996 nd, 0.101
217 0.274, nd 997 nd, 0.175
218 0.279, nd 998 nd, 0.0277
219 0.284, nd 999 nd, 0.0166
220 0.293, nd 1000 nd, 0.0391
221 0.295, nd 1001 nd, 0.00157
222 0.297, nd 1002 nd, 0.0426
223 0.302, nd 1003 nd, 0.0489
224 0.317, nd 1004 nd, 0.0461
225 0.333, nd 1005 nd, 0.0385
226 0.339, nd 1006 nd, 0.0252
227 0.359, nd 1007 nd, 0.0598
228 0.359, nd 1008 nd, 0.0349
229 0.361, nd 1009 nd, 0.0266
230 0.369, nd 1010 nd, 0.114
231 0.414, nd 1011 nd, 0.0264
232 0.42, nd 1012 nd, 0.0923
233 0.43, nd 1013 nd, 0.389
234 0.43, nd 1014 nd, 0.00661
235 0.455, nd 1015 nd, 0.00631
236 0.457, nd 1016 nd, 0.00375
237 0.46, nd 1017 nd, 0.00201 238 0.504, nd 1018 nd, 0.0244
239 0.519, nd 1019 nd, 0.00144
240 0.52, nd 1020 nd, 10.0
241 0.523, nd 1021 nd, 1.17
242 0.524, nd 1022 nd, 0.0135
243 0.543, nd 1023 nd, 0.0127
244 0.574, nd 1024 nd, 0.0921
245 0.585, nd 1025 nd, 0.00795
246 0.618, nd 1026 nd, 0.035
247 0.624, nd 1027 nd, 0.0842
248 0.738, nd 1028 nd, 0.0519
249 0.778, nd 1029 nd, 0.035
250 0.78, nd 1030 nd, 0.0116
251 0.83, nd 1031 nd, 0.0251
252 0.837, nd 1032 nd, 0.156
253 0.852, nd 1033 nd, 0.113
254 0.877, nd 1034 nd, 0.164
255 0.969, nd 1035 nd, 0.376
256 1.23, nd 1036 nd, 0.20
257 1.36, nd 1037 nd, 0.048
258 1.52, nd 1038 nd, 0.0248
259 1.54, nd 1039 nd, 0.105
260 1.57, 0.152 1040 nd, 0.0163
261 1.63, nd 1041 nd, 0.0128
262 1.66, nd 1042 nd, 0.00968
263 1.66, nd 1043 nd, 0.00489
264 1.92, nd 1044 nd, 0.00621
265 2.24, nd 1045 nd, 0.00924
266 2.29, nd 1046 nd, 0.0469
267 2.75, nd 1047 nd, 0.0542
268 2.85, nd 1048 nd, 0.0345
269 3.62, nd 1049 nd, 0.0398
270 4.7, nd 1050 nd, 0.102
271 11.1, nd 1051 nd, 0.0626
272 0.0816, nd 1052 nd, 0.0318
273 1.0, nd 1053 nd, 0.0764
274 1.03, nd 1054 nd, 0.0563
275 0.197, nd 1055 nd, 1.55
276 0.298, nd 1056 nd, 0.335
277 1.02, nd 1057 nd, 2.32
278 0.385, nd 1058 nd, 1.12
279 1.91, nd 1059 nd, 0.394
280 0.04453, 0.0612 1060 nd, 1.57
281 0.0383, nd 1061 nd, 1.78
282 0.14, nd 1062 nd, 0.222
283 0.387, nd 1063 nd, 0.00988
284 0.0333, 0.0344 1064 nd, 0.0621
285 0.00192, 0.00259 1065 nd, 0.00445
286 0.00206, nd 1066 nd, 0.318
287 0.00435, nd 1067 nd, 0.738
288 0.00447, nd 1068 nd, 0.365
289 0.00743, nd 1069 nd, 0.122
290 0.0104, nd 1070 nd, 0.332 291 0.0277, nd 1071 nd, 0.993
292 0.0361, nd 1072 nd, 0.117
293 0.00877, nd 1073 nd, 0.0659
294 0.00814, nd 1074 nd, 0.0674
295 0.0141, nd 1075 nd, 0.0931
296 0.0247, nd 1076 nd, 0.0389
297 0.012, nd 1077 nd, 0.0069
298 0.097, nd 1078 nd, 0.00347
299 0.00673, nd 1079 nd, 0.0259
300 0.0103, nd 1080 nd, 0.00297
301 0.0546, nd 1081 nd, 0.00682
302 0.0157, nd 1082 nd, 0.0195
303 0.251, nd 1083 nd, 0.0117
304 0.0133, nd 1084 nd, 0.0296
305 0.0121, nd 1085 nd, 0.029
306 0.0133, nd 1086 nd, 0.0152
307 0.0254, nd 1087 nd, 0.00733
308 0.0808, nd 1088 nd, 0.0155
309 0.0634, nd 1089 nd, 0.0771
310 0.0368, nd 1090 nd, 0.0493
311 0.00524, nd 1091 nd, 0.0289
312 0.114, nd 1092 nd, 0.0192
313 0.00541, 0.00587 1093 nd, 0.0117
314 0.021, nd 1094 nd, 0.044
315 0.00762, nd 1095 nd, 0.0118
316 0.287, nd 1096 nd, 0.028
317 0.0421, nd 1097 nd, 0.0756
318 0.249, nd 1098 nd, 0.0111
319 0.0319, nd 1099 nd, 0.145
320 0.272, nd 1100 nd, 0.0263
321 0.203, nd 1101 nd, 0.0448
322 0.0255, nd 1102 nd, 0.108
323 0.0988, nd 1103 nd, 0.00784
324 0.333, nd 1104 nd, 1.69
325 0.0987, nd 1105 nd, 0.0619
326 0.0743, nd 1106 nd, 0.364
327 0.223, nd 1107 nd, 0.152
328 0.331, nd 1108 nd, 0.0061
329 2.02, nd 1109 nd, 0.048
330 0.00618, nd 1110 nd, 0.0151
331 0.00611, nd 1111 nd, 0.0139
332 0.0042, nd 1112 nd, 0.0498
333 0.00315, nd 1113 nd, 0.00326
334 0.0223, nd 1114 nd, 0.0281
335 0.00669, nd 1115 nd, 0.0188
336 0.0259, nd 1116 nd, 0.0419
337 0.0261, nd 1117 nd, 0.0332
338 0.0785, nd 1118 nd, 0.00548
339 0.315, nd 1119 nd, 0.0224
340 0.783, nd 1120 nd, 0.0227
341 0.101, nd 1121 nd, 0.0302
342 0.103, nd 1122 nd, 0.162
343 0.0791, nd 1123 nd, 0.0309 344 0.216, nd 1124 nd, 0.0143
345 0.84, nd 1125 nd, 0.0764
346 0.0498, nd 1126 nd, 0.311
347 0.297, nd 1127 nd, 0.00569
348 1.56, nd 1128 nd, 0.199
349 0.0022, nd 1129 nd, 0.546
350 0.00825, nd 1130 nd, 0.0354
351 0.064, nd 1131 nd, 0.0414
352 1.19, nd 1132 nd, 0.201
353 0.00763, nd 1133 nd, 0.703
354 0.0405, nd 1134 nd, 0.175
355 0.124, nd 1135 nd, 0.121
356 0.404, nd 1136 nd, 0.0498
357 9.88, nd 1137 nd, 0.0119
358 0.0711, nd 1138 nd, 0.0874
359 0.0881, nd 1139 nd, 0.333
360 0.239, nd 1140 nd, 0.138
361 0.436, nd 1141 nd, 0.0099
362 0.578, nd 1142 nd, 0.136
363 2.04, nd 1143 nd, 0.328
364 6.48, nd 1144 nd, 0.00515
365 11.2, nd 1145 nd, 0.00619
366 3.34, nd 1146 nd, 0.0148
367 4.84, nd 1147 nd, 0.00824
368 0.00373, nd 1148 nd, 0.0409
369 0.00656, nd 1149 nd, 0.0824
370 0.0075, nd 1150 nd, 0.0132
371 0.0395, nd 1151 nd, 0.048
372 0.0535, nd 1152 nd, 0.233
373 0.0234, nd 1153 nd, 0.00492
374 nd, nd 1154 nd, 0.00962
375 0.595, nd 1155 nd, 0.033
376 nd, nd 1156 nd, 0.216
377 0.105, nd 1157 nd, 0.0725
378 0.492, 0.377 1158 nd, 0.0125
379 0.0511, 0.0404 1159 nd, 0.0179
380 nd, 0.201 1160 nd, 0.237
381 0.547, nd 1161 nd, 0.0044
382 0.257, nd 1162 nd, 0.00954
383 1.99, 1.34 1163 nd, 0.0174
384 0.00974, 0.00889 1164 nd, 0.00544
385 0.040, 0.0484 1165 nd, nd
386 0.0707, nd 1166 nd, 0.0562
387 0.17, nd 1167 nd, 0.0298
388 5.7, 4.55 1168 nd, nd
389 0.266, nd 1169 nd, 0.239
390 0.727, 0.616 1170 nd, 0.0214
391 0.0465, 1.41 1171 nd, 0.0105
392 0.282, 0.288 1172 nd, 0.00867
393 0.415, 0.281 1173 nd, 0.0437
394 2.07, 1.45 1174 nd, 0.0156
395 1.84, 1.67 1175 nd, 0.00662
396 0.474, 0.278 1176 nd, 0.00915 397 0.405, 0.353 1177 nd, 0.0496
398 0.346, 0.272 1178 nd, 0.112
399 0.0903, 0.0736 1179 nd, 0.0791
400 1.89, 2.35 1180 nd, 0.0102
401 0.072, nd 1181 nd, 0.128
402 0.183, nd 1182 nd, nd
403 0.606, nd 1183 nd, 0.0404
404 0.0277, nd 1184 nd, 0.109
405 0.012, nd 1185 nd, 0.0503
406 0.011, nd 1186 nd, 0.0106
407 0.00145, nd 1187 nd, 0.00878
408 0.372, nd 1188 nd, 0.00494
409 1.02, nd 1189 nd, 0.0291
410 0.0295, nd 1190 nd, 0.0843
411 0.0197, nd 1191 nd, 0.0607
412 0.168, 0.109 1192 nd, 0.17
413 2.01, nd 1193 nd, 0.00776
414 0.032, nd 1194 nd, 0.171
415 0.0121, nd 1195 nd, 0.0205
416 0.041, nd 1196 nd, 0.0102
417 4.91, nd 1197 nd, 0.101
418 0.506, 0.0514 1198 nd, nd
419 0.010, nd 1199 nd, 0.165
420 0.0182, nd 1200 nd, nd
421 0.0404, nd 1201 nd, 0.0422
422 3.94, nd 1202 nd, 0.0227
423 12.5, nd 1203 nd, 0.378
424 0.0826, nd 1204 nd, 0.0772
425 0.0814, nd 1205 nd, 0.345
426 0.0104, nd 1206 nd, 0.394
427 0.0154, nd 1207 nd, 0.283
428 0.0327, nd 1208 nd, 0.028
429 0.179, nd 1209 nd, 0.0387
430 0.191, nd 1210 nd, 0.0192
431 0.0607, nd 1211 nd, 0.879
432 0.00874, nd 1212 nd, 0.144
433 0.00807, nd 1213 nd, nd
434 0.0507, nd 1214 nd, 0.035
435 0.00589, nd 1215 nd, 0.133
436 0.00933, nd 1216 nd, 0.054
437 0.0080, nd 1217 nd, 0.0316
438 0.60, nd 1218 nd, 0.158
439 1.69, nd 1219 nd, 0.0613
440 0.0355, nd 1220 nd, 0.0181
441 0.0237, 0.015 1221 nd, 1.13
442 0.0492, nd 1222 nd, 0.0513
443 0.365, nd 1223 nd, 0.0192
444 0.281, nd 1224 nd, 0.497
445 0.0141, nd 1225 nd, 0.0767
446 0.011, nd 1226 nd, 0.0116
447 0.0466, nd 1227 nd, 0.0534
448 0.021, nd 1228 nd, 0.418
449 0.0257, nd 1229 nd, 0.393 450 1.03, nd 1230 nd, 0.0674
451 0.000946, 0.00124 1231 nd, 0.576
452 0.0512, nd 1232 nd, 0.0248
453 0.0527, nd 1233 nd, 0.351
454 0.0803, nd 1234 nd, 0.0174
455 12.2, nd 1235 nd, 0.0668
456 0.0598, 0.0475 1236 nd, 0.078
457 0.0756, nd 1237 nd, 0.561
458 nd, nd 1238 nd, 0.748
459 0.00362, nd 1239 nd, 0.328
460 0.0193, nd 1240 nd, 0.592
461 nd, 0.00815 1241 nd, 0.0122
462 0.00694, nd 1242 nd, 0.0488
463 0.0215, 0.013 1243 nd, 0.142
464 0.0166, 0.0272 1244 nd, 2.23
465 0.00823, 0.0238 1245 nd, 0.0214
466 nd, nd 1246 nd, 0.803
467 0.0165, 0.047 1247 nd, 0.212
468 0.00339, 0.00726 1248 nd, 0.373
469 0.00597, 0.00947 1249 nd, 0.17
470 0.00445, 0.0080 1250 nd, 0.335
471 0.00811, 0.019 1251 nd, 0.111
472 0.0149, 0.0107 1252 nd, 0.125
473 0.00321, 0.00381 1253 nd, 0.669
474 0.00389, 0.00775 1254 nd, 0.00222
475 0.0090, 0.0139 1255 nd, 0.00211
476 0.0125, 0.0468 1256 nd, 0.00328
477 0.00996, nd 1257 nd, 0.00482
478 0.015, 0.386 1258 nd, 0.00831
479 nd, 0.00399 1259 nd, 0.00191
480 0.00571, 0.0676 1260 nd, 0.00491
481 nd, nd 1261 nd, 0.0583
482 0.00511, nd 1262 nd, 0.109
483 0.00479, 0.00937 1263 nd, 0.0116
484 nd, nd 1264 nd, 0.309
485 0.00557, 0.0118 1265 nd, 0.0393
486 0.0047, 0.00497 1266 nd, 0.113
487 0.00884, 0.0573 1267 nd, 0.285
488 0.00825, 0.0211 1268 nd, 0.932
489 0.0123, nd 1269 nd, 0.216
490 0.0212, 0.028 1270 nd, 0.0109
491 0.00455, 0.0113 1271 nd, 0.0627
492 0.0396, 0.0417 1272 nd, 0.0224
493 0.0336, 0.013 1273 nd, 0.132
494 0.016, 0.021 1274 nd, 0.199
495 0.0516, 0.0607 1275 nd, 0.097
496 0.0139, 0.0257 1276 nd, 0.0269
497 0.00331, 0.0048 1277 nd, 0.0429
498 0.307, nd 1278 nd, 0.0136
499 0.806, nd 1279 nd, 0.00784
500 0.182, nd 1280 nd, 0.00438
501 0.0459, 0.018 1281 nd, 0.00122
502 0.157, nd 1282 nd, 0.00134 503 0.0786, nd 1283 nd, 0.00151
504 0.0766, 0.0563 1284 nd, 0.00172
505 0.0204, 0.0182 1285 nd, 0.0432
506 0.0332, 0.0227 1286 nd, 0.00323
507 0.186, nd 1287 nd, 0.00325
508 0.184, nd 1288 nd, 0.0228
509 0.211, nd 1289 nd, 0.0267
510 0.0337, 0.0221 1290 nd, 0.409
511 0.0176, 0.0275 1291 nd, 0.00847
512 0.0436, 0.0443 1292 nd, 0.0252
513 0.0539, 0.0681 1293 nd, 0.0165
514 0.0481, 0.0673 1294 nd, 0.0327
515 0.0723, 0.0666 1295 nd, 0.0607
516 0.0106, 0.00847 1296 nd, 0.0175
517 0.0758, nd 1297 nd, 0.0238
518 0.266, nd 1298 nd, 0.032
519 0.0968, nd 1299 nd, 0.0424
520 0.0488, nd 1300 nd, 0.0111
521 0.0601, 0.0631 1301 nd, 0.0197
522 0.0296, 0.0611 1302 nd, 0.0734
523 0.187, nd 1303 nd, 0.209
524 0.115, nd 1304 nd, 0.204
525 0.0375, 0.060 1305 nd, 0.431
526 0.076, 0.0644 1306 nd, 0.224
527 0.0168, 0.0243 1307 nd, 0.401
528 0.0521, 0.0454 1308 nd, 0.139
529 0.103, nd 1309 nd, 0.0767
530 0.124, nd 1310 nd, nd
531 0.159, nd 1311 nd, 0.0917
532 0.488, nd 1312 nd, 0.0265
533 0.294, nd 1313 nd, 0.0783
534 0.14, nd 1314 nd, 0.0247
535 0.743, nd 1315 nd, 0.214
536 0.187, nd 1316 nd, 0.379
537 0.0132, 0.0106 1317 nd, 0.074
538 0.072, 0.0829 1318 nd, 0.0456
539 0.072, 0.0417 1319 nd, 0.0147
540 0.137, nd 1320 nd, 0.0163
541 0.225, nd 1321 nd, 0.0148
542 0.00277, 0.0026 1322 nd, nd
543 0.00213, 0.00302 1323 nd, nd
544 0.00302, 0.00305 1324 nd, 0.0779
545 0.00278, 0.0020 1325 nd, 0.0903
546 0.00332, 0.00322 1326 nd, 0.0216
547 nd, nd 1327 nd, 1.46
548 nd, nd 1328 nd, 0.147
549 nd, nd 1329 nd, 0.0143
550 nd, nd 1330 nd, 0.0179
551 nd, nd 1331 nd, 0.206
552 nd, nd 1332 nd, 0.0414
553 0.00755, 0.00582 1333 nd, 0.0195
554 0.00401, 0.00519 1334 nd, nd
555 0.0196, 0.0114 1335 nd, 0.0855 556 0.0145, 0.0102 1336 nd, 0.0746
557 0.862, 1.98 1337 nd, 0.105
558 1.84, 5.63 1338 nd, 0.0244
559 1.98, nd 1339 nd, 0.0202
560 5.02, nd 1340 nd, 0.257
561 0.268, nd 1341 nd, 0.195
562 0.0189, 0.0177 1342 nd, 0.0269
563 0.00166, 0.00361 1343 nd, 0.0114
564 0.00196, 0.00159 1344 nd, 0.0821
565 0.0083, 0.00737 1345 nd, 0.183
566 0.193, nd 1346 nd, 0.275
567 0.00675, 0.00624 1347 nd, 0.0292
568 0.00412, 0.00501 1348 nd, 0.0565
569 0.00808, 0.0085 1349 nd, 0.029
570 0.00913, 0.00995 1350 nd, 0.0149
571 0.0138, 0.0104 1351 nd, 0.0184
572 0.00845, 0.00972 1352 nd, 0.0113
573 1.26, nd 1353 nd, 0.00584
574 0.0794, 0.0621 1354 nd, 0.00438
575 0.0538, 0.0378 1355 nd, 0.00307
576 0.0902, 0.0507 1356 nd, 0.00784
577 0.00439, 0.00297 1357 nd, 0.0082
578 0.060, 0.0707 1358 nd, 0.013
579 0.00314, 0.00247 1359 nd, 0.0129
580 0.00239, 0.00201 1360 nd, 0.00654
581 0.0040, 0.00338 1361 nd, 0.00515
582 0.00205, 0.00169 1362 nd, 0.0055
583 0.00282, 0.0027 1363 nd, 0.00534
584 0.0147, 0.0117 1364 nd, 0.0149
585 nd, 0.0271 1365 nd, 0.0119
586 nd, 0.0338 1366 nd, 0.0476
587 nd, 0.444 1367 nd, 0.0291
588 nd, 0.739 1368 nd, 0.0151
589 nd, 0.044 1369 nd, 0.056
590 nd, 0.0428 1370 nd, 0.00237
591 nd, 0.661 1371 nd, 0.0176
592 nd, 0.0884 1372 nd, 0.0106
593 nd, 0.0269 1373 nd, 0.0937
594 nd, 0.021 1374 nd, nd
595 nd, 0.0651 1375 nd, 0.436
596 nd, 0.00448 1376 nd, 0.381
597 nd, 0.0631 1377 nd, 0.275
598 nd, 0.0322 1378 nd, nd
599 nd, 0.0582 1379 nd, 0.0867
600 nd, 0.0385 1380 nd, 0.0936
601 nd, 0.0326 1381 nd, 0.189
602 nd, 0.0392 1382 nd, 0.237
603 nd, 0.056 1383 nd, 0.225
604 nd, 0.0224 1384 nd, 0.0123
605 nd, 0.00759 1385 nd, 0.00676
606 nd, 0.0139 1386 nd, 0.0815
607 nd, 0.00159 1387 nd, 0.0275
608 nd, 0.00985 1388 nd, 0.00403 609 nd, 0.196 1389 nd, 0.00592
610 nd, 1.3 1390 nd, 0.0148
611 nd, 0.328 1391 nd, 0.00956
612 nd, 0.365 1392 nd, nd
613 nd, 0.119 1393 nd, 0.0129
614 nd, 0.0482 1394 nd, nd
615 nd, 0.0842 1395 nd, 0.0176
616 nd, 0.097 1396 nd, 0.00585
617 nd, 1.13 1397 nd, nd
618 nd, 0.00755 1398 nd, 0.0559
619 nd, 0.0827 1399 nd, 0.179
620 nd, 0.00755 1400 nd, 0.0241
621 nd, 0.0118 1401 nd, 0.018
622 nd, 0.0595 1402 nd, 0.0412
623 nd, 1.48 1403 nd, 0.0322
624 nd, 0.046 1404 nd, 0.0561
625 nd, 0.0107 1405 nd, 0.127
626 nd, 0.00759 1406 nd, 0.194
627 nd, 0.164 1407 nd, 0.227
628 nd, 0.0234 1408 nd, 0.222
629 nd, 0.0335 1409 nd, 0.0823
630 nd, 0.0725 1410 nd, 0.0722
631 nd, 0.0506 1411 nd, 0.135
632 nd, 0.104 1412 nd, nd
633 nd, 0.0873 1413 nd, 0.364
634 nd, 0.0361 1414 nd, 0.00826
635 nd, 0.129 1415 nd, 0.0111
636 nd, 1.21 1416 nd, 0.00622
637 nd, 0.0542 1417 nd, 0.0125
638 nd, 0.102 1418 nd, 0.0113
639 nd, 0.0882 1419 nd, 0.0116
640 nd, 0.135 1420 nd, nd
641 nd, 0.163 1421 nd, 0.00753
642 nd, 0.507 1422 nd, 0.0069
643 nd, 0.0633 1423 nd, 0.00831
644 nd, 0.0594 1424 nd, 0.0135
645 nd, 0.125 1425 nd, 0.035
646 nd, 0.00568 1426 nd, 0.0267
647 nd, 0.0385 1427 nd, 0.033
648 nd, 0.845 1428 nd, 0.0184
649 nd, 0.0445 1429 nd, 0.0069
650 nd, 0.106 1430 nd, 0.266
651 nd, 0.0207 1431 nd, 0.011
652 nd, 0.00488 1432 nd, nd
653 nd, 0.0144 1433 nd, 0.0587
654 nd, 0.0256 1434 nd, 0.0574
655 nd, 0.0224 1435 nd, 0.0266
656 nd, 0.116 1436 nd, 0.0484
657 nd, 0.0533 1437 nd, 0.0738
658 nd, 0.00549 1438 nd, 0.0276
659 nd, 0.00585 1439 nd, nd
660 nd, 0.0221 1440 nd, nd
661 nd, 0.00253 1441 nd, 0.032 662 nd, 0.00977 1442 nd, 0.0136
663 nd, 0.0136 1443 nd, 0.0148
664 nd, 0.00412 1444 nd, 0.00577
665 nd, 0.00814 1445 nd, 0.0128
666 nd, 0.0111 1446 nd, 0.0113
667 nd, 0.00905 1447 nd, 0.0105
668 nd, 0.00698 1448 nd, 0.0223
669 nd, 0.0136 1449 nd, 0.0186
670 nd, 0.0183 1450 nd, 0.0154
671 nd, 0.0238 1451 nd, 0.0139
672 nd, 0.011 1452 nd, 0.00765
673 nd, 0.0248 1453 nd, 0.0617
674 nd, 0.00839 1454 nd, 0.0678
675 nd, 0.0414 1455 nd, 0.124
676 nd, 0.0165 1456 nd, 0.0422
677 nd, 0.0126 1457 nd, 0.0715
678 nd, 0.00265 1458 nd, 0.0764
679 nd, 0.00461 1459 nd, 0.0669
680 nd, 0.126 1460 nd, 0.126
681 nd, 0.0603 1461 nd, 0.0487
682 nd, 0.019 1462 nd, 0.0694
683 nd, 0.0669 1463 nd, 0.0779
684 nd, 0.0153 1464 nd, 0.109
685 nd, 0.0205 1465 nd, 0.101
686 nd, 0.653 1466 nd, 0.0125
687 nd, 0.0238 1467 nd, 0.0164
688 nd, 0.00303 1468 nd, 0.00486
689 nd, 0.0123 1469 nd, 0.0138
690 nd, 0.00616 1470 nd, 0.00221
691 nd, 0.0392 1471 nd, 0.0109
692 nd, 0.0247 1472 nd, 0.0125
693 nd, 0.0264 1473 nd, 0.00872
694 nd, 0.0359 1474 nd, 0.00888
695 nd, 0.027 1475 nd, 0.00744
696 nd, 0.00223 1476 nd, 0.21
697 nd, 0.0049 1477 nd, 0.0452
698 nd, 0.0327 1478 nd, 0.0682
699 nd, 0.00558 1479 nd, 0.0015
700 nd, 0.0204 1480 nd, 0.00425
701 nd, 0.0227 1481 nd, 0.00416
702 nd, 0.0232 1482 nd, 0.00488
703 nd, 0.0829 1483 nd, nd
704 nd, 0.0126 1484 nd, 0.00149
705 nd, 0.00742 1485 nd, 0.00323
706 nd, 0.00581 1486 nd, 0.00137
707 nd, 0.00573 1487 nd, 0.00234
708 nd, 0.00997 1488 nd, 0.00844
709 nd, 0.00601 1489 nd, 0.00656
710 nd, 0.00336 1490 nd, nd
711 nd, 0.0462 1491 nd, nd
712 nd, 0.0453 1492 nd, 0.00153
713 nd, 0.0529 1493 nd, 0.00295
714 nd, 0.121 1494 nd, 0.00202 715 nd, 0.136 1495 nd, 0.00877
716 nd, 0.102 1496 nd, 0.00844
717 nd, 0.0718 1497 nd, 0.00135
718 nd, 0.012 1498 nd, 0.00228
719 nd, 0.0347 1499 nd, 0.00152
720 nd, 0.164 1500 nd, 0.00415
721 nd, 0.14 1501 nd, 0.00264
722 nd, 0.00157 1502 nd, 0.0101
723 nd, 0.0209 1503 nd, 0.0067
724 nd, 0.0851 1504 nd, 0.0101
725 nd, 0.477 1505 nd, nd
726 nd, 0.577 1506 nd, 0.00219
727 nd, 1.22 1507 nd, nd
728 nd, 0.00752 1508 nd, 0.00244
729 nd, 0.0445 1509 nd, 0.00397
730 nd, 0.45 1510 nd, 0.00326
731 nd, 0.0183 1511 nd, 0.00664
732 nd, 0.0241 1512 nd, nd
733 nd, 0.0598 1513 nd, 0.0028
734 nd, 0.0845 1514 nd, 0.00183
735 nd, 0.126 1515 nd, 0.00159
736 nd, 0.281 1516 nd, 0.00457
737 nd, 0.186 1517 nd, 0.00103
738 nd, 0.00417 1518 nd, 0.00155
739 nd, 0.0049 1519 nd, 0.00168
740 nd, 0.204 1520 nd, 0.00203
741 nd, 0.0165 1521 nd, 0.0019
742 nd, 0.0331 1522 nd, 0.0316
743 nd, 0.00971 1523 nd, 0.0134
744 nd, 0.00446 1524 nd, 0.00324
745 nd, 0.00868 1525 nd, 0.0063
746 nd, 0.0768 1526 nd, 0.00714
747 nd, 0.00434 1527 nd, 0.0026
748 nd, 0.00455 1528 nd, 0.00881
749 nd, 0.0161 1529 nd, 0.00174
750 nd, 0.0118 1530 nd, 0.00389
751 nd, 0.229 1531 nd, 0.124
752 nd, 0.0108 1532 nd, 0.00541
753 nd, 0.0655 1533 nd, 0.0102
754 nd, 0.0683 1534 nd, 0.0213
755 nd, 0.0407 1535 nd, 0.0201
756 nd, 0.0488 1536 nd, 0.0114
757 nd, 0.00201 1537 nd, 0.0118
758 nd, 0.0293 1538 nd, 0.0257
759 nd, 0.00581 1539 nd, 0.0611
760 nd, 0.00483 1540 nd, 0.0644
761 nd, 0.0131 1541 nd, 0.031
762 nd, 0.0173 1542 nd, 0.762
763 nd, 0.00528 1543 nd, 0.20
764 nd, 0.0581 1544 nd, 0.193
765 nd, 0.0532 1545 nd, 0.774
766 nd, 0.0468 1546 nd, 0.0241
767 nd, 0.169 1547 nd, 0.00501 768 nd, 0.13 1548 nd, 0.000973
769 nd, 0.0695 1549 nd, 0.00471
770 nd, 0.135 1550 nd, 0.0112
771 nd, 0.0893 1551 nd, 0.00472
772 nd, 0.0534 1552 nd, 0.00086
773 nd, 0.297 1553 nd, 0.0216
774 nd, 0.0826 1554 nd, 0.0385
775 nd, 0.0951 1555 nd, 0.0104
776 nd, 0.00746 1556 nd, 0.0488
777 nd, 0.00625 1557 nd, 0.0058
778 nd, 0.0259 1558 nd, 0.0165
779 nd, 0.0385 1559 nd, 0.0447
780 nd, 0.109 1560 nd, 0.0655 nd = not determined
ROCK2 Kinase Activity Assays
assay: ROCK2 activity was initially determined using a radioactive FlashPlate- based assay. In a 96-well format, biotinylated peptide substrates (2μΜ final; S6-short for ROCK2), ^[33P]-ATP (5 μΜ, 2 mCi/μιηοΙ), compounds (0.1-10000 nM in 2% DMSO), and ROCK2 (0.2nM; Upstate) catalytic domains.
HTRF assay: This assay used the CisBio HTRF KinEASE kit(kit 62ST2PEZ) and the kinase reaction containing 0.2 μΜ biotinylated substrate peptide (S2, CisBio), 5 μΜ, 100 μΜ or 1 mM of ATP, inhibitors (0.1 - 10,000 nM in 2% DMSO) and enzymes as in the 33P-ATP assay above.
TABLE 2 shows the results of the HTRF assay and the utility of compounds having Formula I to functionally inhibit ROCK2.
Table 2
Figure imgf000621_0001
380 0.0023 397 0.138
381 0.00412 398 0.0022
382 0.00614 399 nd
383 0.00361 400 0.0251
384 0.00424 547 0.179
385 0.00651 548 0.014
386 10 549 0.0031
387 0.00139 550 0.0154
388 0.0112 551 0.0184
389 0.00174 552 3.27
390 0.00245
nd = not determined
Compounds which inhibit NAMPT are useful for treating diseases in which activation of NF-KB is implicated. Such methods are useful in the treatment of a variety of diseases including inflammatory and tissue repair disorders; particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes,
glomerulonephritis, cancer, particularly wherein the cancer is selected from breast, prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas, leukaemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia.
Involvement of NAMPT in the treatment of cancer is described in WO 97/48696.
Involvement of NAMPT in immuno-supression is described in WO 97/48397. Involvement of NAMPT for the treatment of diseases involving angiogenesis is described in WO
2003/80054. Involvement of NAMPT for the treatment of rheumatoid arthritis and septic shock is described in WO 2008/025857. Involvement of NAMPT for the prophlaxis and treatment of ischaemia is described in WO 2009/109610. Cancers include, but are not limited to, hematologic and solid tumor types such as acoustic neuroma, acute leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute t-cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer (including estrogen-receptor positive breast cancer), bronchogenic carcinoma, Burkitt's lymphoma, cervical cancer,
chondrosarcoma, chordoma, choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocytic) leukemia, chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, dysproliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen-receptor positive breast cancer, essential thrombocythemia, Ewing' s tumor, fibrosarcoma, gastric carcinoma, germ cell testicular cancer, gestational trophobalstic disease, glioblastoma, head and neck cancer, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, hormone insensitive prostate cancer, leiomyosarcoma, liposarcoma, lung cancer (including small cell lung cancer and non-small cell lung cancer), lymphangioendothelio-sarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (lymphoma, including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin's lymphoma and non-Hodgkin's lymphoma), malignancies and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoid malignancies of T-cell or B-cell origin, leukemia, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, peripheral T-cell lymphoma, pinealoma, polycythemia vera, prostate cancer (including hormone-insensitive (refractory) prostate cancer), rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung carcinoma, solid tumors (carcinomas and sarcomas), stomach cancer, squamous cell carcinoma, synovioma, sweat gland carcinoma, testicular cancer (including germ cell testicular cancer), thyroid cancer, Waldenstrom's macroglobulinemia, testicular tumors, uterine cancer, Wilms' tumor and the like.
Abnormal activation of the Rho ROCK pathway has been observed in various disorders (Wettschureck, N., Offermanns, S., Rho/Rho-kinase mediated signaling in physiology and pathophysiology. J. Mol. Med. 80, 2002, 629-638; Miiller, B.K., Mack, H., Teusch, N., Rho kinase, a promising drug target for neurological discorders. Nat. Drug Discov. Rev. 4, 2005, 387-398; Hu, E, Lee, D., ROCK inhibitors as potential therapeutic agents for cardiovascular diseases. Curr. Opin. Investig. Drugs. 4, 2003, 1065-1075). As already mentioned, ROCKs phosphorylate the myosin binding subunit of myosin light chain (MLC) phosphatase (MLCP), resulting in increased myosin phosphorylation and actin- myosin contraction (Somlyo, A.P., Somlyo, A.V., Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev.83, 2003, 1325-1358). Examples of disease states related with abnormal Rho/ROCK activity, in particular with vasospasm activity, include cardiovascular diseases such as hypertension (Satoh S., Kreutz R., Wilm C, Ganten D., Pfitzer G., Augmented agonist- induced Ca2+-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells. J. Clin. Invest. 94, 1994, 1397-1403; Mukai, Y., Shimokawa, H., Matoba, T., Kandabashi, T., Satoh, S., Hiroki, J., Kaibuchi, K., Takeshita, A., Involvement of Rho-kinase in hypertensive vascular disease: a novel therapeutic target in hypertension. FASEB J. 15, 2001,1062-1064; Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M., Narumiya, S., Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 1997, 990-994; Masumoto, A., Hirooka, Y., Shimokawa, H., Hironaga, K., Setoguchi, S., Takeshita, A., Possible involvement of Rhokinase in the pathogenesis of hypertension in humans. Hypertension 38, 2001, 1307-1310), chronic and congestive heart failure (Fuster, V., Badimon, L., Badimon, JJ, Chesebro, JH, The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 326, 1992, 310-318; Shimokawa, H., Cellular and molecular mechanisms of coronary artery spasm: lessons from animal models. Jpn Circ J 64, 2000, 1- 12; Shimokawa, H., Morishige, K., Miyata, K., Kandabashi, T., Eto, Y., Ikegaki, I., Asano, T., Kaibuchi, K., Takeshita, A., Longterm inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo. Cardiovasc Res 51, 2001, 169— 177; Utsunomiya, T., Satoh, S., Ikegaki, I., Toshima, Y., Asano, T., Shimokawa, H.,
Antianginal effects of hydroxyfasudil, a Rho-kinase inhibitor, in a canine model of effort angina. Br J Pharmacol 134, 201, 1724-1730), cardiac hypertrophy (Hoshijima, M., Sah, V.P., Wang, Y., Chien, K.R., Brown, J.H., The low molecular weight GTPase Rho regulates myofibril formation and organization in neonatal rat ventricular myocytes. Involvement of Rho kinase. J Biol Chem 273, 1998, 7725-77230; Sah, V.P., Hoshijima, M., Chien, K.R., Brown, J.H., Rho is required for Galphaq and alpha 1 -adrenergic receptor signal- 637 ing in cardiomyocytes. Dissociation of Ras and Rho pathwaysJ Biol Chem 271, 1996, 31185-1190; Kuwahara, K., Saito, Y., Nakagawa, O., Kishimoto, I., Harada, M., Ogawa, E., Miyamoto, Y., Hamanaka, I., Kajiyama, N., Takahashi, N., Izumi, T., Kawakami, R., Tamura, N., Ogawa, Y., Nakao, K., The effects of the selective ROCK inhibitor, Y27632, on ET- 1 -induced hypertrophic response in neonatal rat cardiacmyocytes-possible involvement of Rho ROCK pathway in cardiac muscle cell hypertrophy. FEBS Lett 452, 1999, 314-318), chronic renal failure (Sharpe, C.C., Hendry, B., M. Signaling: focus on Rho in renal disease. J. Am. Soc. Nephrol. 14, 2003, 261-264), cerebral vasospasm after subarachnoid bleeding (Shibuya, M., Suzuki, Y., Sugita, K., Saito, I., Sasaki, T., Takakura, K., Okamoto, S., Kikuchi, H., Takemae, T., Hidaka, H., Dose escalation trial of a novel calcium antagonist, AT877, in patients 636 with aneurysmal subarachnoid haemorrhage. Acta Neurochir (Wien) 107, 1990, 11-15; Shibuya, M., Suzuki, Y., Sugita, K., Saito, I., Sasaki, T., Takakura, K., Nagata, I., Kikuchi, H., Takemae, T., Hidaka, H., et. al, Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double- blind trial. J Neurosurg 76, 1992, 571-577; Sato, M., Tani, E., Fujikawa, H., Kaibuchi, K., Involvement of Rho-kinase-mediated phosphorylation of myosin light chain in enhancement of cerebral vasospasm. Circ Res 87, 2000, 195-200; Miyagi, Y., Carpenter, R.C., Meguro, T., Parent, A.D., Zhang, J.H., Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage. J Neurosurg 93, 2000, 471^176; Tachibana, E., Harada, T., Shibuya, M. Saito, K., Takayasu, M., Suzuki, Y., Yoshida, J., Intra-arterial infusion of fasudil hydrochloride for treating vasospasm following subarachnoid haemorrhage. Acta Neurochir (Wien) 141, 1999, 13-19), pulmonary hypertension (Sylvester, J.T., Am. J. Physiol. Lung Cell. Mol. Physiol. 287, 2004, L624-L630) and ocular hypertension (Honjo, M., Inatani, M., Kido, N., Sawamura, T., Yue, B.Y., Honda, Y., Tanihara ,H., Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes. Arch Ophthalmol 119, 2001, 1171-1178; Rao, P..V, Deng, P.F.,
Kumar, J. Epstein, D.L., Modulation of aqueous humor outflow facility by the Rho kinase- specific inhibitor Y-27632. Invest Ophthalmol Vis Sci 42, 2001, 1029-1037). Further diseases related to abnormal Rho ROCK activity are cancer (Aznar, S., Fernandez- Valeron, P., Espina, C, Lacal, J.C., Rho GTPases: potential candidates for anticancer therapy. Cancer Lett. 206, 2004, 181-191; Yin, L. et al., Fasudil inhibits vascular endothelial growth factor- induced angiogenesis in vitro and in vivo. Mol Cancer Ther 5, 2007, 1517-25; Itoh, K., Yoshioka, K., Akedo, H., Uehata, M., Ishizaki, T., Narumiya, S., An essential part for Rho- associated kinase in the transcellular invasion of tumor cells. Nat Med 5, 1999, 221-225; Genda, T. Sakamoto, M., Ichida, T., Asakura, H., Kojiro,M., Narumiya, S., Hirohashi, S., Cell motility mediated by rho and Rho-associated protein kinase plays a critical role inintrahepatic metastasis of human hepatocellular carcinoma. Hepatology 30, 1999, 1027-1036; Somlyo, A.V., Bradshaw, D., Ramos, S., Murphy, C, Myers, C.E., Somlyo, A. P., Rho-kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells.Biochem Biophys Res Commun 269, 2000, 652-659), asthma (Roberts, J.A., Raeburn, D., Rodger, I.W., Thomson, N.C., Comparison of in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine in man. Thorax 39; 1984, 837-843; Chiba, Y., Misawa, M., Characteristics of muscarinic cholinoceptors in airways of antigen-induced airway hyperresponsive rats. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 111, 1995, 351-357; Chiba, Y., Takada, Y., Miyamoto, S., MitsuiSaito, M., Karaki, H., Misawa, M., Augmented acetylcholine-induced, Rho mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats. Br J Pharmacol 127, 1999, 597-600; Chiba, Y., Sakai, H. Misawa, M., Augmented acetylcholine- induced translocation of RhoA in bronchial smooth muscle from antigen-induced airway
hyperresponsive rats. BrJ Pharmacol 133, 2001, 886-890; Iizuka, K., Shimizu, Y.,
Tsukagoshi, H., Yoshii, A., Harada, T. Dobashi, K., Murozono, T., Nakazawa, T., Mori, M., Evaluation of Y-27632, a rho-kinase inhibitor, as a bronchodilator in guinea pigs. Eur J Pharmacol 406, 2000, 273-279), male erectile dysfunctions (Andersson, K. E., Hedlund, P., New directions for erectile dysfunction therapies. Int. J. Impot. Res. 14 (Suppl. 1 ), 2002, S82-S92; Chitaley, K., Wingard, C.J., Clinton Webb, R., Branam, H., Stopper, V.S., Lewis, R.W., Mills, T.M., Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxideindependent pathway. Nat Med 7, 2001, 119-122; Mills, T.M., Chitaley, K., Wingard, C.J., Lewis, R.W., Webb, R.C., Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation. J Appl Physiol 91, 2001, 1269-1273), female sexual dysfunction, overactive bladder syndrome (Peters, S.L. et al., Rho kinase: a target for treating urinary bladder dysfunction. Trends Pharmacol Sci. 27, 2006, 492-7) and preterm labor (Niiro, N., Nishimura, J., Sakihara, C, Nakano, H., Kanaide, H., Up-regulation of rho A and rho-kinase mRNAs in the rat myometrium during pregnancy. Biochem Biophys Res Commun 230, 1997, 356-359; Tahara, M., Morishige, K., Sawada, K., Ikebuchi, Y., Kawagishi, R., Tasaka, K., Murata, Y., RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction.
Endocrinology 143, 2002, 920-929; Kupittayanant, S., Burdyga, T., Wray, S., The effects of inhibiting Rho-associated kinase with Y-27632 on force and intracellular calcium in human myometrium. Pflugers Arch. 443, 2001, 112-114).
Inhibitors of ROCKs have been suggested for use in the treatments of a variety of diseases. They include cardiovascular diseases such as hypertension (Satoh S., Kreutz R., Wilm C, Ganten D., Pfitzer G., Augmented agonist-induced Ca2+-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells. J. Clin. Invest. 94, 1994, 1397-1403; Mukai, Y.,
Shimokawa, H., Matoba, T., Kandabashi, T., Satoh, S., Hiroki, J., Kaibuchi, K., Takeshita, A., Involvement of Rho-kinase in hypertensive vascular disease: a novel therapeutic target in hypertension. FASEB J. 15, 2001,1062-1064; Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M.,
Narumiya, S., Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 1997, 990-994; and Masumoto, A., Hirooka, Y., Shimokawa, H., Hironaga, K., Setoguchi, S., Takeshita, A., Possible involvement of Rhokinase in the pathogenesis of hypertension in humans. Hypertension 38, 2001, 1307- 1310), chronic and congestive heart failure(Fuster, V., Badimon, L., Badimon, JJ, Chesebro, JH, The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 326, 1992, 310-318; Shimokawa, H., Cellular and molecular mechanisms of coronary artery spasm: lessons from animal models. Jpn Circ J 64, 2000, 1-12; Shimokawa, H., Morishige, K., Miyata, K., Kandabashi, T., Eto, Y., Ikegaki, I., Asano, T., Kaibuchi, K., Takeshita, A., Longterm inhibition of Rho -kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo. Cardiovasc Res 51, 2001, 169-177; Utsunomiya, T., Satoh, S., Ikegaki, I., Toshima, Y., Asano, T., Shimokawa, H., Antianginal effects of hydroxyfasudil, a Rho-kinase inhibitor, in a canine model of effort angina. Br J Pharmacol 134, 201, 1724-1730), cardiac hypertrophy), and cardiac hyperttophy(Hoshijima, M., Sah, V.P., Wang, Y., Chien, K.R., Brown, J.H., The low molecular weight GTPase Rho regulates myofibril formation and organization in neonatal rat ventricular myocytes. Involvement of Rho kinase. J Biol Chem 273, 1998, 7725-77230; Sah, V.P., Hoshijima, M., Chien, K.R., Brown, J.H., Rho is required for Galphaq and alpha 1 -adrenergic receptor signal- 637 ing in cardiomyocytes. Dissociation of Ras and Rho pathwaysJ Biol Chem 271, 1996, 31185-1190; Kuwahara, K., Saito, Y., Nakagawa, O., Kishimoto, I., Harada, M., Ogawa, E., Miyamoto, Y., Hamanaka, I., Kajiyama, N., Takahashi, N., Izumi, T., Kawakami, R., Tamura, N., Ogawa, Y., Nakao, K., The effects of the selective ROCK inhibitor, Y27632, on ET-1 -induced hypertrophic response in neonatal rat cardiacmyocytes-possible involvement of Rho ROCK pathway in cardiac muscle cell hypertrophy. FEBS Lett 452, 1999, 314-318), chronic renal failure), chronic renal failure(Sharpe, C.C., Hendry, B., M. Signaling: focus on Rho in renal disease. J. Am. Soc. Nephrol. 14, 2003, 261-264), furthermore cerebral vasospasm after subarachnoid bleeding (Shibuya, M., Suzuki, Y., Sugita, K., Saito, I., Sasaki, T., Takakura, K., Okamoto, S., Kikuchi, H., Takemae, T., Hidaka, H., Dose escalation trial of a novel calcium antagonist, AT877, in patients 636 with aneurysmal subarachnoid haemorrhage. (Acta Neurochir (Wien) 107, 1990, 11-15; Shibuya, M., Suzuki, Y., Sugita, K., Saito, I., Sasaki, T., Takakura, K., Nagata, I., Kikuchi, H., Takemae, T., Hidaka, H., et. al, Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. J Neurosurg 76, 1992, 571-577; Sato, M., Tani, E., Fujikawa, H., Kaibuchi, K., Involvement of Rho-kinase-mediated phosphorylation of myosin light chain in enhancement of cerebral vasospasm. Circ Res 87, 2000, 195-200; Miyagi, Y., Carpenter, R.C., Meguro, T., Parent, A.D., Zhang, J.H., Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage. J Neurosurg 93, 2000, 471-476; Tachibana, E., Harada, T., Shibuya, M. Saito, K., Takayasu, M., Suzuki, Y., Yoshida, J., Intra- arterial infusion of fasudil hydrochloride for treating vasospasm following subarachnoid haemorrhage. Acta Neurochir (Wien) 141, 1999, 13-19), pulmonary hypertension(Sylvester, J.T., Am. J. Physiol. Lung Cell. Mol. Physiol. 287, 2004, L624-L630) and ocular hypertension(Honjo, M., Inatani, M., Kido, N., Sawamura, T., Yue, B.Y., Honda, Y., Tanihara ,H., Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes. Arch Ophthalmol 119, 2001, 1171- 1178; Rao, P..V, Deng, P.F., Kumar, J. Epstein, D.L., Modulation of aqueous humor outflow facility by the Rho kinase- specific inhibitor Y-27632. Invest Ophthalmol Vis Sci 42, 2001, 1029-1037). In addition, because of their muscle relaxing properties, they are also suitable for asthma (Roberts, J.A., Raeburn, D., Rodger, I.W., Thomson, N.C., Comparison of in vivo airway responsiveness and in vitro smooth muscle sensitivity to methacholine in man. Thorax 39; 1984, 837-843; Chiba, Y., Misawa, M., Characteristics of muscarinic cholinoceptors in airways of antigen-induced airway hyperresponsive rats. Comp Biochem Physiol C
Pharmacol Toxicol Endocrinol 111, 1995, 351-357; Chiba, Y., Takada, Y., Miyamoto, S., MitsuiSaito, M., Karaki, H., Misawa, M., Augmented acetylcholine-induced, Rho mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats. Br J Pharmacol 127, 1999, 597-600; Chiba, Y., Sakai, H. Misawa, M., Augmented acetylcholine- induced translocation of RhoA in bronchial smooth muscle from antigen-induced airway hyperresponsive rats. BrJ Pharmacol 133, 2001, 886-890; Iizuka, K., Shimizu, Y., Tsukagoshi, H., Yoshii, A., Harada, T. Dobashi, K., Murozono, T., Nakazawa, T., Mori, M., Evaluation of Y-27632, a rho-kinase inhibitor, as a bronchodilator in guinea pigs. Eur J Pharmacol 406, 2000, 273-279), male erectile dysfunctions(Andersson, K. E.,
Hedlund, P., New directions for erectile dysfunction therapies. Int. J. Impot. Res. 14 (Suppl. 1 ), 2002, S82-S92; Chitaley, K., Wingard, C J., Clinton Webb, R., Branam, H., Stopper, V.S., Lewis, R.W., Mills, T.M., Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxideindependent pathway. Nat Med 7, 2001, 119-122; Mills, T.M., Chitaley, K., Wingard, C.J., Lewis, R.W., Webb, R.C., Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation. J Appl Physiol 91, 2001, 1269-1273), female sexual dysfunction and overactive bladder syndrome(Peters, S.L. et al., Rho kinase: a target for treating urinary bladder dysfunction. Trends Pharmacol Sci. 27, 2006, 492-7) and preterm labor(Niiro, N., Nishimura, J., Sakihara, C, Nakano, H., Kanaide, H., Up-regulation of rho A and rho-kinase mRNAs in the rat myometrium during pregnancy. Biochem Biophys Res Commun 230, 1997, 356-359; Tahara, M., Morishige, K., Sawada, K., Ikebuchi, Y., Kawagishi, R., Tasaka, K., Murata, Y., RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction.
Endocrinology 143, 2002, 920-929; Kupittayanant, S., Burdyga, T., Wray, S., The effects of inhibiting Rho-associated kinase with Y-27632 on force and intracellular calcium in human myometrium. Pflugers Arch. 443, 2001, 112-114). Several recent studies have reported the beneficial effects of ROCK inhibitors in ischemia-reperfusion and myocardial infarction. In these studies, the ROCK inhibitors Y-27632 and fasudil were shown to decrease ischemia- reperfusion injury, myocardial infarct size, and myocardial fibrosis in response to experimental myocardial infarction (MI) and in a rat model of chronic hypertension induced congestive heart failure (see above (Fuster, V., Badimon, L., Badimon, JJ, Chesebro, JH, The pathogenesis of coronary artery disease and the acute coronary syndromes (2). N Engl J Med 326, 1992, 310-318; Shimokawa, H., Cellular and molecular mechanisms of coronary artery spasm: lessons from animal models. Jpn Circ J 64, 2000, 1-12; Shimokawa, H., Morishige, K., Miyata, K., Kandabashi, T., Eto, Y., Ikegaki, L, Asano, T., Kaibuchi, K., Takeshita, A., Longterm inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo. Cardiovasc Res 51, 2001, 169-177; Utsunomiya, T., Satoh, S., Ikegaki, I., Toshima, Y., Asano, T., Shimokawa, H., Antianginal effects of hydroxyfasudil, a Rho-kinase inhibitor, in a canine model of effort angina. Br J Pharmacol 134, 201, 1724- 1730), cardiac hypertrophy) and Masumoto, A., Mohri, M., Shimokaw,a H., Urakami, L., Usui, M., Takeshita, A., Suppression of coronary artery spasm by the rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation 105, 2002, 1545-1547; Shimokawa, H., Iinuma, H., Kishida, H., et al., Antianginal effect of fasudil, a Rho-kinase inhibitor, in patients with stable effort angina: a multicenter study (abstract). Circulation 104[Suppl II], 2001, II691; Morishige K, Shimokawa H, Eto Y, Kandabashi T, Miyata K, Matsumoto Y, Hoshijima M, Kaibuchi K, Takeshita A, Adenovirus-mediated transfer of dominant-negative rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo. Arterioscler Thromb Vase Biol 21 , 2001 , 548-554; Kandabashi T, Shimokawa H, Mukai Y, Matoba T, Kunihiro I, Morikawa K, Ito M, Takahashi S, Kaibuchi K, Takeshita A, Involvement of rho- kinase in agonists-induced contractions of arteriosclerotic human arteries. Arterioscler Thromb Vase Biol 22, 2002, 243-248; Liu MW, Roubin GS, King SB 3rd, Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia.
Circulation 79, 1989, 1374-1387; Shibata R, Kai H, Seki Y, Kato S, Morimatsu M, Kaibuchi K, Imaizumi T, Role of Rho-associated kinase in neointima formation after vascular injury. Circulation 103, 2001, 284-289).
Additionally, ROCKs can interact with other signalling pathways resulting in inhibition of phosphoinositide- 3 kinase (PI-3K), endothelial nitric oxide synthase (eNOS) pathways, and activation of plasminogen activator inhibitor- 1 (PAI-1) which may contribute to endothelial dysfunction like restenosis and atherosclerosis. Thus ROCK inhibitors have been suggested for the treatment of restenosis and atherosclerosis(see above (Morishige K, Shimokawa H, Eto Y, Kandabashi T, Miyata K, Matsumoto Y, Hoshijima M, Kaibuchi K, Takeshita A, Adenovirus-mediated transfer of dominant-negative rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo. Arterioscler Thromb Vase Biol 21,
2001, 548-554; Kandabashi T, Shimokawa H, Mukai Y, Matoba T, Kunihiro I, Morikawa K, Ito M, Takahashi S, Kaibuchi K, Takeshita A, Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic human arteries. Arterioscler Thromb Vase Biol 22, 2002, 243- 248; Liu MW, Roubin GS, King SB 3rd, Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia. Circulation 79, 1989, 1374-1387; Shibata R, Kai H, Seki Y, Kato S, Morimatsu M, Kaibuchi K, Imaizumi T, Role of Rho- associated kinase in neointima formation after vascular injury. Circulation 103, 2001, 284- 289) and Iwasaki, H. et al., High glucose induces plasminogen activator inhibitor- 1 expression through Rho/Rho-kinase-mediated NF-kappaB activation in bovine aortic endothelial cells. Atherosclerosis, 2007, Jan 31).
Vascular intimal thickening in vein grafts after surgery is the major cause of late graft failure. In a study with the ROCK inhibitor fasudil, the intimal thickening and vascular smooth muscle cell (VSMC) proliferation was significantly suppressed, whereas VSMC apoptosis was enhanced in the weeks following the procedure, suggesting that ROCK inhibitors can be used as a therapeutic agent for the prevention of graft (Morishige K, Shimokawa H, Eto Y, Kandabashi T, Miyata K, Matsumoto Y, Hoshijima M, Kaibuchi K, Takeshita A, Adeno virus-mediated transfer of dominant-negative rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo. Arterioscler Thromb Vase Biol 21, 2001, 548-554; Kandabashi T, Shimokawa H, Mukai Y, Matoba T, Kunihiro I, Morikawa K, Ito M, Takahashi S, Kaibuchi K, Takeshita A, Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic human arteries. Arterioscler Thromb Vase Biol 22, 2002, 243- 248; Liu MW, Roubin GS, King SB 3rd, Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia. Circulation 79, 1989, 1374-1387; Shibata R, Kai H, Seki Y, Kato S, Morimatsu M, Kaibuchi K, Imaizumi T, Role of Rho- associated kinase in neointima formation after vascular injury. Circulation 103, 2001, 284- 289).
Injury to the adult vertebrate brain and spinal cord activates ROCKs, thereby causing neurodegeneration and inhibition of neuroregeneration like neurite growth and sprouting (Bito, H., Furuyashiki, T., Ishihara, H., Shibasaki, Y., Ohashi, K., Mizuno, K., Maekawa, M., Ishizaki, T., Narumiya, S., A critical role for a Rho-associated kinase, pl60ROCK, in determining axon outgrowth in mammalian CNS neurons. Neuron 26, 2000, 431—441).
Inhibition of ROCKs results in induction of new axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury) (see above (Peters, S.L. et al., Rho kinase: a target for treating urinary bladder dysfunction. Trends Pharmacol Sci. 27, 2006, 492-7) and Hara, M. et al., Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats. J. Neurosurg. Spine 93, 94-
101; Fournier, A. E., Takizawa, B. T. & Strittmatter, S. M., ROCK inhibition enhances axonal regeneration in the injured CNS. J. Neurosci. 23, 2003, 1416-1423 ; Sung, J. K. et al., A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat. Brain Res. 959, 2003, 29-38; Tanaka, H. et al., Cytoplasmic p21(Cipl/WAFl) enhances axonal regeneration and functional recovery after spinal cord injury in rats. Neuroscience 127, 2004, 155-164). ROCK inhibitors are therefore likely to be useful for regenerative (recovery) treatment of CNS disorders such as spinal cord injury, acute neuronal injury (stroke, traumatic brain injury) (Okamura N et al., Vasodilator effects of fasudil, a Rho-kinase inhibitor, on retinal arterioles in stroke-prone spontaneously hypertensive rats. J Ocul Pharmacol Ther. 23, 2007, 207-12; Yagita Y et al., Rho-kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia. J Neurosci Res. 85, 2007, 2460-9), Parkinson's disease, Alzheimer disease (Pedrini S et al., Modulation of statin-activated shedding of Alzheimer APP ectodomain by ROCK. PLoS Med.2, 2005, 18; Burton A., NSAIDS and Alzheimer's disease: it's only Rock and Rho. Lancet Neurol. 3(1), 2004, 6) and other neurodegenerative disorders. Other neurodegenetarive disorders for which ROCK inhibitors are expected to be useful are Huntington's disease (Shao J, Welch WJ, Diprospero NA, Diamond MI. Phosphorylation of profilin by ROCK1 regulates polyglutamine
aggregation.Mol Cell Biol. 2008 Sep;28(17):5196-208; Shao J, Welch WJ, Diamond MI. ROCK and PRK-2 mediate the inhibitory effect of Y-27632 on polyglutamine aggregation. FEBS Lett. 2008 May 28;582(12):1637-42), spinal muscular atrophy (Bowerman M, Shafey D, Kothary R.. Smn depletion alters profilin II expression and leads to upregulation of the RhoA/ROCK pathway and defects in neuronal integrity.J Mol Neurosci. 2007;32(2): 120-31) and amyotrophic lateral sclerosis. Inhibition of the Rho ROCK pathway has also proved to be efficacious in other animal models of neurodegeneration like stroke(Okamura N et al., Vasodilator effects of fasudil, a Rho-kinase inhibitor, on retinal arterioles in stroke-prone spontaneously hypertensive rats. J Ocul Pharmacol Ther. 23, 2007, 207-12; Yagita Y et al., Rho-kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia. J Neurosci Res. 85, 2007, 2460-9) and in inflammatory and demyelinating diseases like multiple sclerosis (Sun X et al., The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J Neuroimmunol. 180, 2006, 126-34), acute and chronic pain (Inoue, M. et al., Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nature Med. 10, 2004, 712-718; Ramer, L. M., Borisoff, J. F. & Ramer, M. S., Rho-kinase inhibition enhances axonal plasticity and attenuates cold hyperalgesia after dorsal rhizotomy. J Neurosci. 24, 2004, 10796-10805; Tatsumi, S. et al., Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS). Neuroscience 131, 2005, 491-498).
ROCK inhibitors have been shown to possess anti-inflammatory properties by decreased cytokine release, e.g.TNFa. Thus they can be used as treatment for neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease,
Parkinson's disease, amyotrophic lateral sclerosis and inflammatory pain, as well as other inflammatory diseases such as rheumatoid arthritis, osteoarthritis, osteoporosis, asthma, irritable bowel syndrome, or inflammatory bowel disease (Segain J. P., Rho kinase blockade prevents inflammation via nuclear factor kappa B inhibition: evidence in Crohn's disease and experimental colitis. Gastroenterology. 124(5), 2003, 1180-7). In addition, recent reports have demonstrated that inhibition of ROCK results in disruption of inflammatory cell chemotaxis as well as inhibition of smooth muscle contraction in models of pulmonary inflammation associated with asthma. Therefore, the inhibitors of the Rho/ROCK pathway should be useful for the treatment of asthma (see above (Sun X et al., The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J Neuroimmunol. 180, 2006, 126-34) and Kawaguchi A, Ohmori M, Harada K, Tsuruoka S, Sugimoto K, Fujimura A., The effect of a Rho kinase inhibitor Y- 27632 on superoxide production, aggregation and adhesion inhuman polymorphonuclear leukocytes. Eur J Pharmacol 403, 2000, 203-208 ; Lou Z, Billadeau DD, Savoy DN, Schoon RA, Leibson P.J., A role for a RhoA/ROCK/LIM-kinase pathway in the regulation of cytotoxic lymphocytes. J Immunol 167, 2001, 5749-5757; Vicente-Manzanares M, Cabrero JR, Rey M, Perez- Martinez M, Ursa A, Itoh K, Sanchez-Madrid F., A role for the Rho-pl60 Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor- 1 alpha-induced lymphocyte actomyosinand microtubular organization and chemotaxis. J Immunol 168, 2002, 400^110; Thorlacius K et al., Protective effect of fasudil, a Rho-kinase inhibitor, on chemokine expression, leukocyte recruitment, and hepatocellular apoptosis in septic liver injury. J Leukoc Biol. 79, 2006, 923-31).
Since ROCK inhibitors reduce cell proliferation and cell migration, they could be useful in treating cancer and tumor metastasis(Aznar, S., Fernandez- Valeron, P., Espina, C, Lacal, J.C., Rho GTPases: potential candidates for anticancer therapy. Cancer Lett. 206, 2004, 181-191; Yin, L. et al., Fasudil inhibits vascular endothelial growth factor-induced angiogenesis in vitro and in vivo. Mol Cancer Ther 5, 2007, 1517-25.
Itoh, K., Yoshioka, K., Akedo, H., Uehata, M., Ishizaki, T., Narumiya, S., An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med 5, 1999, 221- 225; Genda, T. Sakamoto, M., Ichida, T., Asakura, H., Kojiro,M., Narumiya, S., Hirohashi, S., Cell motility mediated by rho and Rho-associated protein kinase plays a critical role inintrahepatic metastasis of human hepatocellular carcinoma. Hepatology 30, 1999, 1027- 1036; Somlyo, A.V., Bradshaw, D., Ramos, S., Murphy, C, Myers, C.E., Somlyo, A.P., Rho- kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells. Biochem Biophys Res Commun 269, 2000, 652-659). ROCK inhibitors can also be beneficial in diseases with impaired blood brain barrier function, e.g. HIV-1 encephalitis (Persidski Y et al., Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE). Blood. 107, 2006, 4770-4780) and Alzheimer's disease (Man S-M et al., Peripheral T cells overexpress MIP-la to enhance its transendothelial migration in Alzheimer's disease. Neurobiol. Of Aging 28, 2007, 485- 496).
Furthermore, there is evidence suggesting that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in antiviral and anti-bacterial applications (Favoreel HW, Cytoskeletal rearrangements and cell extensions induced by the US3 kinase of an alphaherpesvirus are associated with enhanced spread. Proc Natl Acad Sci U S A. 102(25), 2006, 8990-5).
ROCKs have been reported to interfere with insulin signalling through serine phosphorylation of insulin receptor substrate-1 (IRS-1), in cultured VSMC. Activation of Rho A/ROCK was observed in skeletal muscles and aortic tissues of Zucker obese rats.
Inhibition of ROCK, by fasudil for 4 weeks, reduced blood pressure, corrected glucose and lipid metabolism, improved insulin signalling and endothelial dysfunction. In another experiment administration of high dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. ROCK inhibitors may therefore be useful for the treatment of insulin resistance and diabetes (Nakamura Y et al., Marked increase of insulin gene transcription by suppression of the Rho Rho-kinase pathway. Biochem Biophys Res Commun. 350(1), 2006, 68-73; Kikuchi Y et al., A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats. J Endocrinol. 192(3), 2007, 595-603; Goyo A et al., The Rho- kinase inhibitor, fasudil, attenuates diabetic nephropathy in streptozotocin-induced diabetic rats. Eur J Pharmacol. 568(1-3), 2007, 242-7).
The ROCK inhibitor Fasudil increased cerebral blood flow and was neuroprotective under CNS ischemic conditions. ROCK inhibitors are expected to be useful for the treatment of ischemic CNS disorders and may therefore improve functional outcome in patients suffering from stroke, vascular or AD type dementia (Okamura N et al., Vasodilator effects of fasudil, a Rho-kinase inhibitor, on retinal arterioles in stroke-prone spontaneously hypertensive rats. J Ocul Pharmacol Ther. 23, 2007, 207-12; Yagita Y et al., Rho-kinase activation in endothelial cells contributes to expansion of infarction after focal cerebral ischemia. J Neurosci Res. 85, 2007, 2460-9).
Due to the efficacy of Y-27632 and fasudil in animal models of epileptogenesis, ROCK inhibitors have been suggested for the use in the treatments of epilepsy and seizure disorders (Inan SY, Buyukafsar K. Antiepileptic effects of two Rho-kinase inhibitors, Y- 27632 and fasudil, in mice. Br. J. Pharmacol, advance online publication, 9 June 2008;
doi:10.1038/bjp.2008.225) ROCK inhibitors are also expected to be useful for the treatment of glaucoma(Honjo, M., Inatani, M., Kido, N., Sawamura, T., Yue, B.Y., Honda, Y., Tanihara ,H., Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes. Arch Ophthalmol 119, 2001, 1171-1178; Rao, P..V, Deng, P.F., Kumar, J. Epstein, D.L., Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632. Invest Ophthalmol Vis Sci 42, 2001, 1029-1037), psoriasis, retinopathy and benign prostatic hypertrophy.
Furthermore, there is evidence suggesting that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in anti- viral and anti-bacterial applications.
As ROCKs have been implicated in neuronal morphogenesis, connectivity, and plasticity in general, they are expected to be useful for the treatment of psychiatric disorders, e.g. depression, schizophrenia, obsessive compulsive disorder and bipolar disorders.
ROCK inhibitors have been described in e.g. WO 2007/026920, WO 2005/074643, and WO 2004/016597. However, their affinity and selectivity or their pharmacological profile is not yet satisfactory.
Schemes and Experimentals
The following abbreviations have the meanings indicated. ADDP means l,l'-(azodicarbonyl)dipiperidine; AD-mix-β means a mixture of (DHQD)2PHAL, K3Fe(CN)6, K2C03, and K2S04; 9-BBN means 9-borabicyclo(3.3.1)nonane; Boc means
tert-butoxycarbonyl; (DHQD)2PHAL means hydroquinidine 1,4-phthalazinediyl diethyl ether; DBU means l,8-diazabicyclo[5.4.0]undec-7-ene; DIBAL means diisobutylaluminum hydride; DIEA means diisopropylethylamine; DMAP means Ν,Ν-dimethylaminopyridine; DMF means N,N-dimethylformamide; dmpe means l,2-bis(dimethylphosphino)ethane; DMSO means dimethylsulfoxide; dppb means l,4-bis(diphenylphosphino)-butane; dppe means 1,2- bis(diphenylphosphino)ethane; dppf means l,l'-bis(diphenylphosphino)ferrocene; dppm means l,l-bis(diphenylphosphino)methane; EDAC HCl means l-(3-dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride; Fmoc means fluorenylmethoxycarbonyl; HATU means 0-(7-azabenzotriazol- 1 -yl)-N,N'N'N'-tetramethyluronium hexafluorophosphate; HMPA means hexamethylphosphoramide; IPA means isopropyl alcohol; MP-BH3 means macroporous triethylammonium methylpolystyrene cyanoborohydride; TEA means triethylamine; TFA means trifluoroacetic acid; tetrahydrofuran means tetrahydrofuran; NCS means N-chlorosuccinimide; NMM means N-methylmorpholine; NMP means
N-methylpyrrolidine; PPh3 means triphenylphosphine.
The following schemes are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. Compounds of this invention may be made by synthetic chemical processes, examples of which are shown herein. It is meant to be understood that the order of the steps in the processes may be varied, that reagents, solvents and reaction conditions may be substituted for those specifically mentioned, and that vulnerable moieties may be protected and deprotected, as necessary.
Schemes
Figure imgf000635_0001
As shown in Scheme 1 , compounds of formula (1), wherein X1, X2, and X3 are as described herein, can be reacted with methyl 4-isocyanatobenzoate to provide compounds of formula (2). The reaction is typically performed in a solvent such as but not limited to tetrahydrofuran. The methyl 4-isocyanatobenzoate is typically added at low temperature followed by stirring at room temperature. Compounds of formula (3) can be prepared by reacting compounds of formula (2) with aqueous lithium hydroxide. The reaction is typically performed in a solvent such as but not limited to tetrahydrofuran, methanol, or mixtures thereof. Compounds of formula (3) can be reacted with amine of formula (3 A), wherein R5 is hydrogen or is as described herein, using coupling conditions known to those skilled in the art and readily available in the literature to provide compounds of formula (4), which are representative of the compounds of this invention.
Scheme 2
Figure imgf000635_0002
described herein, can be reacted with 4-nitrophenylisocyanate to provide compounds of formula (5). The reaction is typically performed in a solvent such as but not limited to tetrahydrofuran. Compounds of formula (5) can be treated with a hydrogen balloon in the presence of 10% Pd on carbon to provide compounds of formula (6). The reaction is typically performed at ambient temperature in a solvent such as but not limited to dimethylformamide. Compounds of formula (6) can be reacted with acid of formula (6A), wherein R5 is as described herein, using coupling conditions known to those skilled in the art and readily available in the literature to provide compounds of formula (7), which are representative of the compounds of this invention.
Figure imgf000636_0001
As shown in Scheme 3, compounds of formula (1), wherein X1, X2, and X3 are as described herein, can be reacted with 4-bromophenyl isocyanate to provide compounds of formula (8). The reaction is typically performed in a solvent such as but not limited to tetrahydrofuran. Compounds of formula (8) can be reacted with a boronic acid of formula (9 A) (or an appropriate boronate ester), wherein R5 is as described herein, using Suzuki Coupling conditions known to those skilled in the art and readily available in the literature to provide compounds of formula (9), which are representative of the compounds of this invention.
Figure imgf000637_0001
As shown in Scheme 4, compounds of formula (8), wherein X1, X2, and X3 are as described herein, can be reacted with tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)-5,6-dihydropyridine-l(2H)-carboxylate under Suzuki coupling conditions known to those skilled in the art and widely available in the literature to provide compounds of formula (10). Compounds of formula (11) can be prepared by treating compounds of formula (10) with an acid such as but not limited to trifluoroacetic acid. The reaction is typically performed at room temperature in a solvent such as but not limited to dichloromethane. Compounds of formula (11) can be reacted with compounds of formula (12A) wherein R13 is as described herein, in the presence of a carboxyl activating agent such as but not limited to N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, and a coupling agent such but not limited to 1 -hydro xybenzotriazole hydrate, to provide compounds of formula (12). The reaction is typically performed at room temperature in a solvent such as but not limited to N,N-dimethylformamide.
Alternatively, compounds of formula (12) can be treated with hydrogen in the presence of palladium on carbon to provide compounds of formula (13). The reaction is typically performed under pressure in a solvent such as but not limited to tetrahydrofuran or N,N-dimethylformamide. Compounds of formula (13) can be reacted with compounds of formula (12A) wherein R13 is as described herein, in the presence of a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, and a coupling agent such but not limited to 1 -hydroxybenzotriazole hydrate, to provide compounds of formula (14). The reaction is typically performed at room temperature in a solvent such as but not limited to N,N-dimethylformamide.
Figure imgf000638_0001
Aqueous potassium hydroxide and a phase transfer catalyst such as but not limited to tetrabutylammonium bromide can be added to a mixture of 4-hydroxy-l-piperidine-l- carboxylic acid tert-butyl ester and l-fluoro-4-nitrobenzene to provide tert-butyl 4-(4- nitrophenoxy)piperidine- 1 -carboxylate. tert-Butyl 4-(4-aminophenoxy)piperidine- 1 - carboxylate can be prepared by reacting tert-butyl 4-(4-nitrophenoxy)piperidine-l-carboxylate with hydrogen in the presence of palladium on carbon. The reaction is typically performed under pressure in a solvent such as but not limited to tetrahydrofuran or N,N- dimethylformamide. tert-Butyl 4-(4-aminophenoxy)piperidine-l -carboxylate can be reacted with bis(2,5-dioxopyrrolidin-l-yl) carbonate and pyridine in acetonitrile, followed by the addition of a base such as but not limited to diisopropylethylamine and compounds of formula (15A) to provide compounds of formula (15). The reaction is typically performed at room temperature. Compounds of formula (16) can be prepared by treating compounds of formula (15) with an acid such as but not limited to trifluoroacetic acid. The reaction is typically performed at room temperature in a solvent such as but not limited to
dichloromethane. Compounds of formula (16) can be reacted with compounds of formula (12A) wherein R13 is as described herein, in the presence of a carboxyl activating agent such as but not limited to N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, and a coupling agent such but not limited to 1-hydroxybenzotriazole hydrate, to provide compounds of formula (17). The reaction is typically performed at room temperature in a solvent such as but not limited to N,N-dimethylformamide.
The following examples are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. The exemplified compounds were named using ACD/ChemSketch Version 12.01 (13 May 2009), Advanced Chemistry Development Inc., Toronto, Ontario), or ChemDraw® Ver. 9.0.5 (CambridgeSoft, Cambridge, MA). Intermediates were named using ChemDraw® Ver. 9.0.5 (CambridgeSoft, Cambridge, MA).
Experimentals
Example 1
N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 1A
Methyl 4-(isoindoline-2-carboxamido)benzoate Isoindoline (1.693 ml, 14.47 mmol) was dissolved in tetrahydrofuran (20 ml) and cooled to 0°C; and methyl 4-isocyanatobenzoate (2.18 g, 12.06 mmol) was added by syringe and the resulting mixture was warmed to ambient temperature, and then stirred overnight. The solution was concentrated to a slurry, diluted with ether, and filtered to provide the title compound.
Example IB
4-(isoindoline-2-carboxamido)benzoic acid
Methyl 4-(isoindoline-2-carboxamido)benzoate (1.65 g, 5.57 mmol) was dissolved in tetrahydrofuran (30 ml) and methanol (15.00 ml) followed by the addition of lithium hydroxide (11.14 ml, 22.27 mmol) and the mixture was allowed to stir at ambient temperature over the weekend. The organic solvent was removed under vacuum, the aqueous layer was adjusted to pH ~3 with 2N aqueous HC1, and the resulting solid was filtered with water washes to provide the title compound after drying.
Example 1C
N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide 4-(Isoindoline-2-carboxamido)benzoic acid (150 mg, 0.531 mmol) and 1- hydroxybenzotriazole hydrate (122 mg, 0.797 mmol) were dissolved in dimethylformamide (3ml) followed by addition of 3-phenylpropan-l -amine (110 mg, 0.797 mmol) and N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (153 mg, 0.797 mmol). The homogeneous solution was stirred at ambient temperature overnight. The solution was diluted with water to give a precipitate which was filtered, washed with cold ethyl acetate then ether and dried under vacuum to provide the title compound. ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ ppm 8.27-8.34 (bs, 1H), 7.93-7.98 (m, 1H), 7.73-7.76 (m, 2H), 7.61-7.64 (m, 2H), 7.32-7.36 (m, 2H), 7.27-7.32 (m, 2H), 7.24-7.28 (m, 2H), 7.19-7.24 (m, 2H), 7.13-7.18 (m, 1H), 4.79 (s, 4H), 3.30 (q, J = 6.5 Hz, 2H), 2.65 (t, 7 = 7.6 Hz, 2H), 1.86 (p, J = 7.3 Hz, 2H); MS (ESI(+)) m/e 400 (M+H)+. Example 2
N-(4-{ [4-(aminomethyl)benzyl]carbamoyl}phenyl)-5-fluoro-1 -dihydro-2H-isoindole-2- carboxamide
Example 2A
methyl 4-(5-fluoroisoindoline-2-carboxamido)benzoate
The title compound was prepared as described in Example 1A, substituting 5- fluoroisoindoline for isoindoline.
Example 2B
4-(5 -fluoroisoindoline-2-carboxamido)benzoic acid The title compound was prepared as described in Example IB, substituting methyl 4-
(5-fluoroisoindoline-2-carboxamido)benzoate for methyl 4-(isoindoline-2- carboxamido)benzoate.
Example 2C
tert-butyl 4-((4-(5-fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate The title compound was prepared as described in Example 1C, substituting 4-(5- fluoroisoindoline-2-carboxamido)benzoic acid for 4-(isoindoline-2-carboxamido)benzoic acid and tert-butyl 4-(aminomethyl)benzylcarbamate for 3-phenylpropan-l-amine.
Example 2D
N-(4-{ [4-(aminomethyl)benzyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide
tert-Butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate (392 mg, 0.756 mmol) was dissolved in dichloromethane, treated with trifluoroacetic acid (582 μΐ, 7.56 mmol), stirred for 3 hours at ambient temperature and then concentrated to dryness. The resulting solid was triturated with ether, collected and dried under vacuum to provide the title compound. ¾ NMR (400 MHz, DMSO-d6) δ ppm 4.01 (q, 7=5.6 Hz, 2 H), 4.46 (d, 7=6.0 Hz, 2 H), 4.76 (d, 7=7.9 Hz, 4 H), 7.08 - 7.29 (m, 2 H), 7.32 - 7.44 (m, 5 H), 7.67 (d, 7=8.7 Hz, 2 H), 7.76 - 7.86 (m, 2 H),8.12 (s, 2 H), 8.63 (s, 1 H), 8.91 (t, 7=6.2 Hz, 1 H); MS (ESI(+)) m/e 419 (M+H)+.
Table 3.
The following Examples were prepared essentially as described in Example 1, substituting the appropriate substituted isoindoline for isoindoline in Example 1A and the appropriate amine for 3-phenylpropan-l-amine in Example 1C. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC; some compounds also required Boc-deprotection after amide coupling as described in Example 2D. Accordingly, some Examples were isolated as trifluoroacetic acid salts.
Figure imgf000640_0001
Figure imgf000641_0001
Figure imgf000642_0001
Figure imgf000643_0001
Figure imgf000644_0001
Figure imgf000645_0001
Figure imgf000646_0001
dihydro-2H- 7.28-7.38 (m, 3H), 7.22-7.27 (m, 3H), 7.11- isoindole-2- 7.19 (m, IH), 5.31 (s, 2H), 4.70-4.85 (m, 4H) carboxamide
N-(4-{ [4-(pyridin-2- ¾ NMR (400 MHz, DMSO-d6/Deuterium (ESI(+)) yl)piperazin-l- Oxide, Temp=90°C) δ ppm 8.08 (ddd, 7 = m/e 428 yl] carbonyl jphenyl)- 5.4, 1.9, 0.8 Hz, IH), 7.77 (ddd, 7 = 8.9, 7.0, (M+H)+ l,3-dihydro-2H- 1.9 Hz, IH), 7.65-7.68 (m, 2H), 7.38-7.42
isoindole-2- (m, 2H), 7.32-7.39 (m, 4H), 7.03-7.06 (m,
carboxamide IH), 6.83 (ddd, 7 = 7.0, 5.4, 0.8 Hz, IH),
4.82 (s, 4H), 3.64-3.72 (m, 8H)
N-(4-{ [4-(pyrazin-2- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+)) yl)piperazin-l- Oxide) δ ppm 8.33-8.34 (bs, IH), 8.13-8.14 m/e 429 yl] carbonyl jphenyl)- (bs, IH), 7.88-7.89 (bs, IH), 7.65-7.67 (m, (M+H)+ l,3-dihydro-2H- 2H), 7.38-7.42 (m, 2H), 7.37-7.40 (m, 2H), isoindole-2- 7.31-7.36 (m, 2H), 4.79-4.80 (bs, 4H), 3.52- carboxamide 3.75 (m, 8H)
N-(4-{ [4-(2- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) methoxyphenyl)piper Temp=90°C) δ ppm 8.30-8.32 (bs, IH), 7.92- m/e 457 azin-1- 7.96 (m, 2H), 7.56-7.59 (m, 2H), 7.20-7.23 (M+H)+ yl] carbonyl jphenyl)- (m, 2H), 7.16-7.19 (m, 2H), 6.97-7.03 (m,
l,3-dihydro-2H- IH), 6.90-6.96 (m, 3H), 4.86 (s, 4H), 3.78- isoindole-2- 3.81 (m, 4H), 3.75 (s, 3H), 3.04-3.07 (m, 4H) carboxamide
N-{4-[(3,3- ¾ NMR (500 MHz, DMSO- ) δ ppm 8.56 (ESI(+)) dimethylbutyl)carba (s, IH), 8.20 (t, 7 = 5.7 Hz, IH), 7.74-7.76 m/e 366 moyl] phenyl } - 1 , 3 - (m, 2H), 7.64-7.66 (m, 2H), 7.34-7.40 (m, (M+H)+ dihydro-2H- 2H), 7.29-7.34 (m, 2H), 4.78-4.79 (bs, 4H), isoindole-2- 3.24-3.28 (m, 2H), 1.43-1.46 (m, 2H), 0.93 carboxamide (s, 9H)
N-(4-{ [(2R)- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) tetrahydrofuran-2 - Temp=90°C) δ ppm 8.33 (d, 7 = 8.7 Hz, IH), m/e 366 ylmethyl]carbamoyl} 8.08-8.10 (m, 2H), 7.90-7.96 (bs, IH), 7.89- (M+H)+ phenyl)- 1 ,3-dihydro- 7.93 (m, 2H), 7.19-7.24 (m, 2H), 7.14-7.18
2H-isoindole-2- (m, 2H), 4.84 (s, 4H), 4.10-4.19 (m, IH),
carboxamide 3.74-3.83 (m, 2H), 3.56-3.67 (m, 2H), 1.79- 1.91 (m, IH), 1.56-1.80 (m, 3H)
N-(4-{ [4-(3- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) methoxyphenyl)piper Temp=90°C) δ ppm 8.32-8.33 (bs, IH), 7.93- m/e 457 azin-1- 7.96 (m, 2H), 7.55-7.58 (m, 2H), 7.15-7.27 (M+H)+ yl] carbonyl jphenyl)- (m, 5H), 6.63 (t, 7 = 2.3 Hz, IH), 6.60 (ddd, l,3-dihydro-2H- 7 = 8.2, 2.4, 0.8 Hz, IH), 6.54 (ddd, 7 = 8.1, isoindole-2- 2.3, 0.8 Hz, IH), 4.86 (s, 4H), 3.72-3.76 (m, carboxamide 4H), 3.71 (s, 3H), 3.14-3.17 (m, 4H)
N-(4-{ [4-(4- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) acetylphenyl)piperazi Temp=90°C) δ ppm 8.34 (d, 7 = 2.2 Hz, IH), m/e 469 n-1- 7.98-8.02 (m, 2H), 7.93-7.96 (m, 2H), 7.56- (M+H)+ yl] carbonyl jphenyl)- 7.60 (m, 2H), 7.20-7.26 (m, 2H), 7.15-7.20 l,3-dihydro-2H- (m, 2H), 6.89-6.93 (m, 2H), 4.87 (s, 4H),
isoindole-2- 3.73-3.76 (m, 4H), 3.26-3.32 (m, 4H), 2.47 carboxamide (s, 3H)
N-(4-{ [2-(2,3- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) dimethoxypheny 1) eth Temp=90°C) δ ppm 8.25-8.26 (bs, IH), 8.08- m/e 446 yl]carbamoyl}phenyl 8.13 (bs, IH), 8.07-8.11 (m, 2H), 7.89-7.92 (M+H)+ )-l,3-dihydro-2H- (m, 2H), 7.19-7.23 (m, 2H), 7.17-7.19 (m, isoindole-2- 2H), 6.93-6.97 (m, 1H), 6.91 (dd, 7 = 7.6, 2.0 carboxamide Hz, 1H), 6.82 (dd, J = 7.7, 1.9 Hz, 1H), 4.84
(s, 4H), 3.85-3.89 (m, 2H), 3.83 (s, 3H), 3.70
(s, 3H), 3.11 (t, 7 = 7.2 Hz, 2H)
N-{4-[(3- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) thienylmethyl)c arb a Temp=90°C) δ ppm 8.54-8.60 (m, 1H), 8.27- m/e 378 moyl] phenyl } - 1 , 3 - 8.31 (bs, 1H), 8.12-8.14 (m, 2H), 7.90-7.93 (M+H)+ dihydro-2H- (m, 2H), 7.26-7.30 (m, 2H), 7.19-7.23 (m,
isoindole-2- 2H), 7.16-7.19 (m, 3H), 4.84 (s, 4H), 4.77 (d, carboxamide 7 = 5.8 Hz, 2H)
5-methoxy-N-{4-[(3- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.55 (ESI(+)) methylbutyl)carbamo (s, 1H), 8.22 (t, 7 = 5.6 Hz, 1H), 7.73-7.78 m/e 382 yl] phenyl} -1,3 - (m, 2H), 7.62-7.67 (m, 2H), 7.26 (d, 7 = 8.3 (M+H)+ dihydro-2H- Hz, 1H), 6.94 (d, 7 = 2.0 Hz, 1H), 6.89 (dd, 7
isoindole-2- = 8.3, 2.4 Hz, 1H), 4.70-4.75 (m, 4H), 3.77 carboxamide (s, 3H), 3.22-3.30 (m, 2H), 1.53-1.69 (m,
1H), 1.37-1.45 (m, 2H), 0.91 (d, 7 = 6.6 Hz,
6H)
N-{4-[(pyridin-2- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.93 (ESI(+)) ylmethyl)carbamoyl] (t, 7 = 6.0 Hz, 1H), 8.61 (s, 1H), 8.51 (ddd, 7 m/e 372 phenyl } - 1 , 3 -dihydro - = 4.8, 1.8, 0.9 Hz, 1H), 7.83-7.87 (m, 2H), (M+H)+ 2H-isoindole-2- 7.75 (td, 7 = 7.7, 1.8 Hz, 1H), 7.67-7.72 (m, carboxamide 2H), 7.29-7.40 (m, 5H), 7.26 (ddd, 7 = 7.5,
4.8, 1.1 Hz, 1H), 4.80 (s, 4H), 4.56 (d, 7 =
5.8 Hz, 2H)
5-fluoro-N-(4-{ [2-(2- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.60 (ESI(+)) thienyl) ethyl] c arb am (s, 1H), 8.45 (t, 7 = 5.6 Hz, 1H), 7.74-7.78 m/e 410 oyl}phenyl)-l,3- (m, 2H), 7.63-7.67 (m, 2H), 7.40 (dd, 7 = (M+H)+ dihydro-2H- 8.4, 5.2 Hz, 1H), 7.33 (dd, 7 = 5.0, 1.3 Hz, isoindole-2- 1H), 7.24 (dd, 7 = 9.1, 2.3 Hz, 1H), 7.10- carboxamide 7.19 (m, 1H), 6.96 (dd, 7 = 5.0, 3.4 Hz, 1H),
6.90-6.93 (m, 1H), 4.71-4.84 (m, 4H), 3.44- 3.53 (m, 2H), 3.06 (t, 7 = 7.2 Hz, 2H)
N-(4-{ [(2S)- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) tetrahydrofuran-2 - Temp=90°C) δ ppm 8.27-8.31 (bs, 1H), 8.06- m/e 366 ylmethyl]carbamoyl} 8.12 (m, 2H), 7.89-7.93 (m, 2H), 7.89-7.92 (M+H)+ phenyl)- 1 ,3-dihydro- (m, 1H), 7.18-7.25 (m, 2H), 7.14-7.19 (m,
2H-isoindole-2- 2H), 4.84 (s, 4H), 4.14 (qd, 7 = 6.7, 4.5 Hz, carboxamide 1H), 3.73-3.83 (m, 2H), 3.55-3.68 (m, 2H),
1.80-1.91 (m, 1H), 1.56-1.79 (m, 3H)
N-(4-{ [l-(3- ¾ NMR (300 MHz, DMSO- ) δ ppm 10.21 (ESI(+)) methylbutyl)-lH- (s, 1H), 8.63 (s, 1H), 8.03 (d, 7 = 0.7 Hz, m/e 418 pyrazol-4- 1H), 7.85-7.89 (m, 2H), 7.70-7.74 (m, 2H), (M+H)+ yl]carbamoyl}phenyl 7.56 (d, 7 = 0.7 Hz, 1H), 7.30-7.40 (m, 4H),
)-l,3-dihydro-2H- 4.80 (s, 4H), 4.10 (t, 7 = 7.1 Hz, 2H), 1.65
isoindole-2- (q, 7 = 7.0 Hz, 2H), 1.40-1.56 (m, 1H), 0.90 carboxamide (d, 7 = 6.6 Hz, 6H)
4-chloro-N-(4-{ [4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.66 (ESI(+))
(pyridin-2- (s, 1H), 8.13 (dd, 7 = 4.9, 1.9 Hz, 1H), 7.64- m/e 462 yl)piperazin-l- 7.71 (m, 2H), 7.56 (ddd, 7 = 8.7, 7.0, 1.9 Hz, (M+H)+ yl] carbonyl jphenyl)- 1H), 7.34-7.41 (m, 5H), 6.85 (d, 7 = 8.6 Hz, l,3-dihydro-2H- 1H), 6.67 (dd, 7 = 6.9, 4.8 Hz, 1H), 4.76- isoindole-2- 4.92 (m, 4H), 3.45-3.74 (m, 8H)
carboxamide
Figure imgf000649_0001
Figure imgf000650_0001
Figure imgf000651_0001
N-(4-{ [4-(pyrazin-2- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.65 (ESI(-)) yl)piperazin-l- (s, IH), 8.34 (s, IH), 8.09-8.12 (bs, IH), 7.87 m/e 495 yl] carbonyl jphenyl)- (d, 7 = 2.6 Hz, IH), 7.76-7.78 (bs, IH), 7.64- (M-H)"
89 5-(trifluoromethyl)- 7.73 (m, 3H), 7.58-7.64 (m, IH), 7.37-7.41
l,3-dihydro-2H- (m, 2H), 4.85-4.88 (bs, 4H), 3.62-3.65 (m,
isoindole-2- 8H)
carboxamide
N-(4-{ [2-(2,5- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(-)) dimethoxypheny 1) eth Oxide) δ ppm 7.73-7.75 (m, 2H), 7.62-7.65 m/e 444 yl]carbamoyl}phenyl (m, 2H), 7.37-7.40 (m, 2H), 7.32-7.35 (m, (M-H)"
90
)-l,3-dihydro-2H- 2H), 6.90 (d, 7 = 8.6 Hz, IH), 6.76-6.78 (m, isoindole-2- 2H), 4.78-4.80 (bs, 4H), 3.78 (s, 3H), 3.44 (t, carboxamide 7 = 7.3 Hz, 2H), 2.81 (t, 7 = 7.2 Hz, 2H)
N-{4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.58 (ESI(+))
[(tetrahydrofuran-3- (s, IH), 8.39 (t, 7 = 5.7 Hz, IH), 7.75-7.79 m/e 366 ylmethyl)carbamoyl] (m, 2H), 7.65-7.68 (m, 2H), 7.30-7.39 (m, (M+H)+
91 phenyl } - 1 , 3 -dihydro - 4H), 4.79 (s, 4H), 3.57-3.78 (m, 3H), 3.48
2H-isoindole-2- (dd, 7 = 8.5, 5.2 Hz, IH), 3.17-3.28 (m, 2H), carboxamide 2.41-2.51 (m, IH), 1.93 (dtd, 7 = 12.2, 8.0,
5.7 Hz, IH), 1.54-1.66 (m, IH)
N- {4- [(1 -benzyl- 1H- ¾ NMR (300 MHz, DMSO- ) δ ppm 10.25 (ESI(+)) pyrazol-4- (s, IH), 8.63 (s, IH), 8.11 (s, IH), 7.84-7.88 m/e 438 yl)carbamoyl]phenyl (m, 2H), 7.70-7.74 (m, 2H), 7.61 (d, 7 = 0.7 (M+H)+
92
}-l,3-dihydro-2H- Hz, IH), 7.23-7.40 (m, 9H), 5.31 (s, 2H),
isoindole-2- 4.79-4.80 (bs, 4H)
carboxamide
methyl 5-({4-[(l,3- ¾ NMR (400 MHz, Pyridine-^, (APCI(+) dihydro-2H-isoindol- Temp=90°C) δ ppm 10.25-10.26 (bs, IH), ) m/e 456
2- 8.92 (d, 7 = 1.9 Hz, IH), 8.34-8.36 (bs, IH), (M+H)+
93 ylc arbonyl) amino] be 8.23-8.25 (m, 2H), 8.17 (dd, 7 = 8.9, 2.0 Hz,
nzo yl } amino) - 1 H - IH), 7.95-7.98 (m, 2H), 7.64 (d, 7 = 8.9 Hz, indazole-3- IH), 7.20-7.24 (m, 2H), 7.15-7.20 (m, 2H),
carboxylate 4.86 (s, 4H), 3.90 (s, 3H)
N-(4-{ [2-(2- ¾ NMR (400 MHz, DMSO-^ Deuterium (ESI(+)) oxopyrrolidin-1- Oxide, Temp=90°C) δ ppm 7.73-7.75 (m, m/e 393 yl)ethyl]carbamoyl}p
94 2H), 7.62-7.65 (m, 2H), 7.32-7.40 (m, 4H), (M+H)+ henyl) - 1 , 3 - dihydro - 4.82 (s, 4H), 3.38-3.47 (m, 6H), 2.23 (t, 7 =
2H-isoindole-2- 8.0 Hz, 2H), 1.91-1.99 (m, 2H)
carboxamide
N-{4-[(pyridin-4- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) ylmethyl)carbamoyl] Temp=90°C) δ ppm 8.81-8.88 (m, IH), 8.57- m/e 373 phenyl } - 1 , 3 -dihydro - 8.60 (m, 2H), 8.34-8.37 (bs, IH), 8.16-8.19 (M+H)+
95
2H-isoindole-2- (m, 2H), 7.94-7.98 (m, 2H), 7.30-7.32 (m,
carboxamide 2H), 7.19-7.23 (m, 2H), 7.17-7.19 (m, 2H),
4.85 (s, 4H), 4.74 (d, 7 = 6.0 Hz, 2H)
N-(4-{ [4-(5- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.56 (ESI(+)) chloropyridin-2- (s, IH), 8.13 (d, 7 = 2.7 Hz, IH), 7.64-7.70 m/e 462 yl)piperazin-l- (m, 2H), 7.63 (dd, 7 = 9.2, 2.7 Hz, IH), 7.30- (M+H)+
96 yl] carbonyl jphenyl)- 7.39 (m, 6H), 6.90 (d, 7 = 9.1 Hz, IH), 4.79- l,3-dihydro-2H- 4.80 (bs, 4H), 3.47-3.72 (m, 8H)
isoindole-2- carboxamide
N-(4-{ [2-(lH-indol- ¾ NMR (400 MHz, DMSO-^ Deuterium (ESI(+))
97
3- Oxide, Temp=90°C) δ ppm 7.75-7.78 (m, m/e 425 yl)ethyl]carbamoyl}p 2H), 7.63-7.66 (m, 2H), 7.59-7.63 (m, 1H), (M+H)+ henyl) - 1 , 3 - dihydro - 7.32-7.40 (m, 5H), 7.17 (s, 1H), 7.10 (ddd, 7
2H-isoindole-2- = 8.1 , 6.9, 1.2 Hz, 1H), 7.01 (ddd, 7 = 7.9,
carboxamide 6.9, 1.0 Hz, 1H), 4.82 (s, 4H), 3.60 (t, 7 = 7.4
Hz, 2H), 3.01 (t, 7 = 7.4 Hz, 2H)
N-(4- { [4- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+))
(trifluoromethyl)benz Oxide) δ ppm 9.05 (t, 7 = 6.0 Hz, 1H), 7.81 - m/e 440 yl]carbamoyl}phenyl 7.84 (m, 2H), 7.66-7.71 (m, 4H), 7.53-7.55 (M+H)+
98
)-l,3-dihydro-2H- (m, 2H), 7.36-7.41 (m, 2H), 7.32-7.36 (m,
isoindole-2- 2H), 4.79-4.80 (bs, 4H), 4.54-4.56 (m, 2H)
carboxamide
N-{4-[(3,5- ¾ NMR (500 MHz, DMSO-^ Deuterium (APCI(+) dimethoxyphenyl)car Oxide) δ ppm 7.88-7.91 (m, 2H), 7.71-7.74 ) m/e 418 bamoyl]phenyl } - 1 ,3- (m, 2H), 7.38-7.41 (m, 2H), 7.33-7.36 (m, (M+H)+
99
dihydro-2H- 2H), 7.06-7.07 (m, 2H), 6.27 (t, 7 = 2.2 Hz,
isoindole-2- 1H), 4.80-4.81 (bs, 4H), 3.78 (s, 6H)
carboxamide
N-{4-[(pyridin-3- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) ylmethyl)carbamoyl] Temp=90°C) δ ppm 8.81 (d, 7 = 2.3 Hz, 1H), m/e 373 phenyl } - 1 , 3 -dihydro - 8.75-8.80 (m, 1H), 8.53 (dd, 7 = 4.7, 1.6 Hz, (M+H)+ 2H-isoindole-2- 1H), 8.31-8.33 (bs, 1H), 8.12-8.15 (m, 2H),
100
carboxamide 7.91-7.94 (m, 2H), 7.71-7.75 (m, 1H), 7.19- 7.23 (m, 2H), 7.16-7.18 (m, 2H), 7.10-7.14
(m, 1H), 4.84 (s, 4H), 4.75 (d, 7 = 5.8 Hz,
2H)
N-[4-(2,3-dihydro- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) l,4-benzodioxin-6- Temp=90°C) δ ppm 9.88-9.89 (bs, 1H), 8.30 m/e 416 ylcarbamoyl)phenyl] (d, J = 2.0 Hz, 1H), 8.13-8.16 (m, 2H), 7.89- (M+H)+
101 -l,3-dihydro-2H- 7.92 (m, 2H), 7.77 (d, 7 = 2.5 Hz, 1H), 7.41
isoindole-2- (dd, 7 = 8.6, 2.5 Hz, 1H), 7.19-7.23 (m, 2H), carboxamide 7.17-7.19 (m, 2H), 6.93 (d, 7 = 8.6 Hz, 1H),
4.84 (s, 4H), 4.07-4.10 (m, 4H)
N-(4- { [4-(2- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+)) fluorobenzoyl)pipera Oxide) δ ppm 7.63-7.65 (m, 2H), 7.50-7.57 m/e 473 zin-1- (m, 1H), 7.42-7.46 (m, 1H), 7.35-7.41 (m, (M+H)+
102 yl] carbonyl jphenyl)- 4H), 7.28-7.35 (m, 4H), 4.78-4.79 (bs, 4H),
l,3-dihydro-2H- 3.71-3.76 (m, 2H), 3.51-3.62 (m, 4H), 3.30- isoindole-2- 3.33 (m, 2H)
carboxamide
N-(4- { [2-(5- ¾ NMR (400 MHz, DMSO-^ Deuterium (ESI(+)) methoxy-lH-indol-3- Oxide, Temp=90°C) δ ppm 7.75-7.78 (m, m/e 455 yl)ethyl]carbamoyl}p 2H), 7.62-7.65 (m, 2H), 7.36-7.41 (m, 2H), (M+H)+ henyl) - 1 , 3 - dihydro - 7.31-7.36 (m, 2H), 7.27 (dd, 7 = 8.7, 0.6 Hz,
103
2H-isoindole-2- 1H), 7.14 (q, 7 = 0.7 Hz, 1H), 7.11 (dd, 7 =
carboxamide 2.4, 0.5 Hz, 1H), 6.76 (dd, 7 = 8.6, 2.4 Hz,
1H), 4.82 (s, 4H), 3.78 (s, 3H), 3.58 (t, 7 =
7.3 Hz, 2H), 2.97 (t, 7 = 7.3 Hz, 2H)
N-{4-[(3- ¾ NMR (400 MHz, Pyridine-^, (APCI(+) aminobenzyl)carbam Temp=90°C) δ ppm 8.39-8.43 (m, 1H), 8.30- ) m/e 387 oyl]phenyl} -l,3- 8.32 (bs, 1H), 8.11-8.14 (m, 2H), 7.90-7.93 (M+H)+
104 dihydro-2H- (m, 2H), 7.20-7.24 (m, 2H), 7.17-7.19 (m,
isoindole-2- 2H), 7.09 (t, 7 = 7.7 Hz, 1H), 6.92 (t, 7 = 1.9 carboxamide Hz, 1H), 6.80 (dd, 7 = 7.5, 1.4 Hz, 1H), 6.67- 6.70 (m, 1H), 4.85 (s, 4H), 4.73 (d, 7 = 5.8
Figure imgf000654_0001
Figure imgf000655_0001
Figure imgf000656_0001
Figure imgf000657_0001
dihydro-2H- 8H), 4.73-4.74 (bs, 4H), 3.20-3.30 (m, 2H), isoindole-2- 2.63 (t, J = 7.6 Hz, 2H), 2.33 (s, 3H), 1.82
carboxamide (p, 7 = 7.4 Hz, 2H)
N-[4-(l,4-dioxa-8- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) azaspiro [4.5] dec- 8 - Temp=90°C) δ ppm 8.27-8.28 (bs, 1H), 7.89- m/e 408 ylcarbonyl)phenyl] - 7.92 (m, 2H), 7.52-7.55 (m, 2H), 7.19-7.23 (M+H)+
138
l,3-dihydro-2H- (m, 2H), 7.16-7.18 (m, 2H), 4.85 (s, 4H),
isoindole-2- 3.84 (s, 4H), 3.73-3.76 (m, 4H), 1.71-1.75
carboxamide (m, 4H)
N-{4-[(2- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.57 (ESI(+)) phenylethyl)c arb amo (s, 1H), 8.38 (t, 7 = 5.6 Hz, 1H), 7.73-7.77 m/e 386 yl] phenyl} -1,3 - (m, 2H), 7.64-7.67 (m, 2H), 7.20-7.39 (m, (M+H)+
139
dihydro-2H- 9H), 4.79 (s, 4H), 3.43-3.50 (m, 2H), 2.80- isoindole-2- 2.88 (m, 2H)
carboxamide
N-(4-{ [2-(2,4- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) dimethoxypheny 1) eth Temp=90°C) δ ppm 8.25-8.26 (bs, 1H), 8.07- m/e 446 yl]carbamoyl}phenyl 8.09 (m, 2H), 7.95-8.02 (m, 1H), 7.88-7.93 (M+H)+
)-l,3-dihydro-2H- (m, 2H), 7.19-7.24 (m, 2H), 7.13-7.19 (m,
140
isoindole-2- 2H), 6.57 (d, 7 = 2.4 Hz, 1H), 6.49 (dd, 7 =
carboxamide 8.1, 2.4 Hz, 1H), 4.84 (s, 4H), 3.81-3.85 (m,
2H), 3.68 (s, 3H), 3.66 (s, 3H), 3.04 (t, 7 =
7.0 Hz, 2H)
N-(4-{ [3- ¾ NMR (400 MHz, DMSO-^ Deuterium (ESI(+))
(methylthio)propyl] c Oxide, Temp=90°C) δ ppm 7.76-7.78 (m, m/e 370 arb amoy 1 } phenyl) - 2H), 7.63-7.65 (m, 2H), 7.32-7.40 (m, 4H), (M+H)+
141
l,3-dihydro-2H- 4.82 (s, 4H), 3.37 (t, 7 = 6.9 Hz, 2H), 2.53- isoindole-2- 2.57 (m, 2H), 2.09 (s, 3H), 1.85 (p, 7 = 7.1
carboxamide Hz, 2H)
N-{4-[(2- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) ethoxyethyl)carbamo Temp=90°C) δ ppm 8.28-8.34 (m, 1H), 8.07- m/e 354 yl] phenyl} -1,3 - 8.12 (m, 2H), 8.01-8.08 (m, 1H), 7.89-7.92 (M+H)+
142 dihydro-2H- (m, 2H), 7.19-7.24 (m, 2H), 7.14-7.18 (m,
isoindole-2- 2H), 4.84 (s, 4H), 3.76 (q, 7 = 5.7 Hz, 2H), carboxamide 3.63 (t, 7 = 5.7 Hz, 2H), 3.43 (q, 7 = 6.9 Hz,
2H), 1.09 (t, 7 = 6.9 Hz, 3H)
N-{4-[(2- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(-)) fluorophenyl)carbam Oxide) δ ppm 7.91-7.93 (m, 2H), 7.72-7.75 m/e 374 oyl]phenyl}-l,3- (m, 2H), 7.56-7.65 (m, 1H), 7.37-7.42 (m, (M-H)"
143
dihydro-2H- 2H), 7.32-7.37 (m, 2H), 7.26-7.31 (m, 2H), isoindole-2- 7.21-7.26 (m, 1H), 4.78-4.82 (m, 4H)
carboxamide
N-(4-{ [2-(pyridin-3- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.57 (ESI(+)) yl)ethyl]carbamoyl}p (s, 1H), 8.45 (d, 7 = 2.2 Hz, 1H), 8.41 (dd, 7 m/e 387 henyl) - 1 , 3 - dihydro - = 4.7, 1.6 Hz, 1H), 8.38 (d, 7 = 5.5 Hz, 1H), (M+H)+
144
2H-isoindole-2- 7.71-7.75 (m, 2H), 7.63-7.68 (m, 3H), 7.29- carboxamide 7.39 (m, 5H), 4.79 (s, 4H), 3.46-3.53 (m,
2H), 2.87 (t, 7 = 7.1 Hz, 2H)
N-[4-({4- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+))
[(trifluoromethyl)thio Oxide) δ ppm 9.03 (t, 7 = 6.0 Hz, 1H), 8.67- m/e 472 ]benzyl } carbamoyl)p 8.70 (bs, 1H), 7.82-7.84 (m, 2H), 7.66-7.70 (M+H)+
145
henyl] - 1 , 3 - dihydro - (m, 4H), 7.47-7.49 (m, 2H), 7.36-7.41 (m,
2H-isoindole-2- 2H), 7.31-7.36 (m, 2H), 4.79-4.80 (bs, 4H), carboxamide 4.53 (d, 7 = 5.3 Hz, 2H)
Figure imgf000659_0001
N- { 4- [( 1 -isopropyl- ¾ NMR (300 MHz, DMSO- ) δ ppm 10.21 (ESI(+)) lH-pyrazol-4- (s, IH), 8.64 (s, IH), 8.03 (d, 7 = 0.7 Hz, m/e 390 yl)carbamoyl]phenyl IH), 7.85-7.89 (m, 2H), 7.70-7.74 (m, 2H), (M+H)+
154
}-l,3-dihydro-2H- 7.57 (d, 7 = 0.7 Hz, IH), 7.30-7.40 (m, 4H), isoindole-2- 4.80-4.81 (bs, 4H), 4.41-4.55 (m, IH), 1.41 carboxamide (d, 7 = 6.7 Hz, 6H)
N-{4-[(4- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) hydroxyphenyl)carba Temp=90°C) δ ppm 9.83-9.85 (bs, IH), 8.29- m/e 374 moyl] phenyl } - 1 , 3 - 8.33 (bs, IH), 8.16-8.18 (m, 2H), 7.91-7.93 (M+H)+
155
dihydro-2H- (m, 2H), 7.86-7.89 (m, 2H), 7.19-7.23 (m,
isoindole-2- 2H), 7.17-7.19 (m, 3H), 7.10-7.12 (m, 2H), carboxamide 4.84 (s, 4H)
N-{4-[(l-ethyl-lH- ¾ NMR (300 MHz, DMSO- ) δ ppm 10.22 (ESI(+)) pyrazol-4- (s, IH), 8.64 (s, IH), 8.03 (s, IH), 7.85-7.90 m/e 376 yl)carbamoyl]phenyl (m, 2H), 7.70-7.74 (m, 2H), 7.57 (s, IH), (M+H)+
156
}-l,3-dihydro-2H- 7.30-7.40 (m, 4H), 4.80-4.81 (bs, 4H), 4.11 isoindole-2- (q, 7 = 7.2 Hz, 2H), 1.36 (t, 7 = 7.2 Hz, 3H) carboxamide
N-{4-[(2,5- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) dimethoxyphenyl)car Temp=90°C) δ ppm 8.97-8.99 (bs, IH), 8.56 m/e 418 bamoyl]phenyl } - 1 ,3- (d, 7 = 3.0 Hz, IH), 8.40-8.42 (bs, IH), 8.07- (M+H)+
157 dihydro-2H- 8.10 (m, 2H), 7.96-7.98 (m, 2H), 7.21-7.24
isoindole-2- (m, 2H), 7.16-7.19 (m, 2H), 6.88 (d, 7 = 8.8 carboxamide Hz, IH), 6.69 (dd, 7 = 8.8, 3.0 Hz, IH), 4.85
(s, 4H), 3.72 (s, 3H), 3.71 (s, 3H)
N-{4-[methyl(3- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.51 (ESI(+)) phenylpropyl)carbam (s, IH), 7.60-7.64 (m, 2H), 7.11-7.44 (m, m/e 414 oyl]phenyl}-l,3- 11H), 4.78-4.79 (bs, 4H), 3.26-3.52 (m, 2H), (M+H)+
158
dihydro-2H- 2.94 (s, 3H), 2.34-2.70 (m, 2H), 1.82-1.91
isoindole-2- (m, 2H)
carboxamide
N-{4-[(2-hydroxy-2- ¾ NMR (400 MHz, Pyridine-^, (ESI(-)) methylpropyl)carbam Temp=90°C) δ ppm 8.30-8.32 (bs, IH), 8.06- m/e 352 oyl]phenyl}-l,3- 8.09 (m, 2H), 7.89-7.95 (m, IH), 7.89-7.92 (M-H)"
159
dihydro-2H- (m, 2H), 7.19-7.23 (m, 2H), 7.15-7.19 (m,
isoindole-2- 2H), 4.84 (s, 4H), 3.70 (d, 7 = 5.9 Hz, 2H), carboxamide 1.38 (s, 6H)
N-(4-{ [4- ¾ NMR (400 MHz, Pyridine-^, (ESI(-))
(trifluoromethyl)pipe Temp=90°C) δ ppm 8.31-8.33 (bs, IH), 7.91- m/e 416 ridin-1- 7.94 (m, 2H), 7.50-7.55 (m, 2H), 7.19-7.24 (M-H)"
160 yl] carbonyl jphenyl)- (m, 2H), 7.15-7.19 (m, 2H), 4.86 (s, 4H),
l,3-dihydro-2H- 4.34-4.39 (m, 2H), 2.83 (td, 7 = 12.9, 2.8 Hz, isoindole-2- 2H), 2.24-2.43 (m, IH), 1.73-1.77 (m, 2H), carboxamide 1.50 (qd, 7 = 12.5, 4.4 Hz, 2H)
N- [4- (thiomorpholin- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) 4- Temp=90°C) δ ppm 8.29-8.31 (bs, IH), 7.90- m/e 368 ylcarbonyl)phenyl] - 7.92 (m, 2H), 7.47-7.50 (m, 2H), 7.20-7.23 (M+H)+
161
l,3-dihydro-2H- (m, 2H), 7.15-7.19 (m, 2H), 4.85 (s, 4H),
isoindole-2- 3.81-3.84 (m, 4H), 2.54-2.58 (m, 4H)
carboxamide
N-[4-(5,6- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.59 (ESI(+)) dihydroimidazo [1,5- (s, IH), 7.67-7.71 (m, 2H), 7.60-7.62 (bs, m/e 388
162
a]pyrazin-7(8H)- IH), 7.30-7.43 (m, 6H), 6.72-6.77 (bs, IH), (M+H)+ ylcarbonyl)phenyl] - 4.79-4.80 (bs, 4H), 4.73-4.75 (bs, 2H), 4.06-
Figure imgf000661_0001
isoindole-2- IH), 4.83 (s, 4H), 1.94 (q, 7 = 7.5 Hz, 2H), carboxamide 1.47 (s, 6H), 0.90 (t, 7 = 7.4 Hz, 3H)
N-(4-{ [2-(lH- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) imidazol-4- Temp=90°C) δ ppm 8.48-8.52 (bs, IH), 8.32- m/e 376 yl)ethyl]carbamoyl}p 8.34 (bs, IH), 8.27 (s, IH), 8.09-8.12 (m, (M+H)+
171
henyl) - 1 , 3 - dihydro - 2H), 7.90-7.93 (m, 2H), 7.19-7.23 (m, 2H),
2H-isoindole-2- 7.16-7.19 (m, 2H), 4.84 (s, 4H), 3.90-3.96
carboxamide (m, 2H), 3.13 (t, J = 6.7 Hz, 2H)
N-(4-{ [(2S)-2- ¾ NMR (400 MHz, Pyridine-^, (ESI(-)) hydroxypropyl] carba Temp=90°C) δ ppm 8.28-8.30 (bs, IH), 8.06- m/e 338 moyl } phenyl) -1,3- 8.10 (m, 2H), 8.03-8.09 (m, IH), 7.88-7.91 (M-H)" dihydro-2H- (m, 2H), 7.19-7.23 (m, 2H), 7.15-7.19 (m,
172
isoindole-2- 2H), 4.84 (s, 4H), 4.25 (dddd, 7 = 12.4, 7.0, carboxamide 6.3, 4.2 Hz, IH), 3.78 (ddd, 7 = 13.4, 6.1, 4.3
Hz, IH), 3.61 (ddd, 7 = 13.4, 6.9, 5.4 Hz,
IH), 1.31 (d, 7 = 6.2 Hz, 3H)
N-(4-{ [(lR)-l-(3- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) cyanophenyl)ethyl] ca Temp=90°C) δ ppm 8.32-8.37 (m, IH), 8.28- m/e 411 rbamoyl jphenyl)- 8.32 (bs, IH), 8.09-8.12 (m, 2H), 7.88-7.90 (M+H)+ l,3-dihydro-2H- (m, 2H), 7.83 (s, IH), 7.69-7.72 (m, IH),
173
isoindole-2- 7.43-7.47 (m, IH), 7.30 (t, 7 = 7.8 Hz, IH), carboxamide 7.19-7.24 (m, 2H), 7.14-7.18 (m, 2H), 5.55
(p, 7 = 7.1 Hz, IH), 4.83 (s, 4H), 1.56 (d, 7 =
7.0 Hz, 3H)
N-(4-{ [(2S)-l- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) hydroxy-3- Temp=90°C) δ ppm 8.29-8.31 (bs, IH), 8.05- m/e 366 methylbutan-2- 8.08 (m, 2H), 7.87-7.90 (m, 2H), 7.46-7.53 (M+H)+
174 yl]carbamoyl}phenyl (bs, IH), 7.19-7.24 (m, 2H), 7.14-7.18 (m,
)-l,3-dihydro-2H- 2H), 4.84 (s, 4H), 4.29-4.36 (m, IH), 3.99 (d, isoindole-2- 7 = 4.8 Hz, 2H), 2.17-2.28 (m, IH), 1.00- carboxamide 1.10 (m, 6H)
N-{4-[benzyl(2- ¾ NMR (400 MHz, Pyridine-^, (ESI(-)) hydroxyethyl)carbam Temp=90°C) δ ppm 8.20-8.21 (bs, IH), 7.85- m/e 414 oyl]phenyl}-l,3- 7.88 (m, 2H), 7.61-7.64 (m, 2H), 7.37-7.43 (M-H)"
175 dihydro-2H- (m, 2H), 7.29-7.34 (m, 2H), 7.20-7.27 (m,
isoindole-2- 3H), 7.14-7.19 (m, 2H), 4.94-4.94 (bs, 2H), carboxamide 4.84 (s, 4H), 3.94-3.97 (m, 2H), 3.73 (t, 7 =
6.0 Hz, 2H)
N-{4-[(4- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(-)) cy anophenyl)c arb am Oxide) δ ppm 7.97-7.99 (m, 2H), 7.91-7.93 m/e 381 oyl]phenyl}-l,3- (m, 2H), 7.80-7.83 (m, 2H), 7.72-7.77 (m, (M-H)"
176
dihydro-2H- 2H), 7.38-7.41 (m, 2H), 7.33-7.36 (m, 2H), isoindole-2- 4.81 (s, 4H)
carboxamide
N-(4-{ [2-(4- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+)) chloropheny 1) ethyl] c Oxide) δ ppm 8.66 (s, IH), 8.45 (t, 7 = 5.6 m/e 420 arb amoy 1 } phenyl) - Hz, IH), 7.72-7.74 (m, 2H), 7.64 (dd, 7 = (M+H)+
177 l,3-dihydro-2H- 8.7, 2.3 Hz, 2H), 7.37-7.40 (m, 2H), 7.32- isoindole-2- 7.36 (m, 4H), 7.27-7.30 (m, 2H), 4.78-4.79 carboxamide (bs, 4H), 3.45-3.50 (m, 2H), 2.84 (t, 7 = 7.2
Hz, 2H)
N-(4-{ [2-(4- ¾ NMR (400 MHz, Pyridine-^, (ESI(+))
178 methylpiperazin- 1 - Temp=90°C) δ ppm 8.34-8.35 (bs, IH), 8.08- m/e 408 yl)ethyl]carbamoyl}p 8.12 (m, 2H), 8.06-8.10 (m, IH), 7.92-7.94 (M+H)+
Figure imgf000663_0001
carboxamide 5.9 Hz, 2H), 2.78 (t, 7 = 6.0 Hz, 2H)
Figure imgf000664_0001
yl]carbamoyl}phenyl 7.31-7.36 (m, 2H), 4.82 (s, 4H), 4.50 (dd, 7 =
)-l,3-dihydro-2H- 9.1, 5.0 Hz, IH), 1.60-1.77 (m, 3H), 0.94
isoindole-2- (dd, 7 = 11.0, 6.1 Hz, 6H)
carboxamide
tert-butyl (l-{4- ¾ NMR (400 MHz, pyridine-d5) δ ppm 1.49 (ESI(+))
[(l,3-dihydro-2H- - 1.51 (m, 9 H), 1.51 - 1.61 (m, 1 H), 1.88 - m/e 465 isoindol-2- 2.00 (m, 1 H), 2.98 - 3.11 (m, 2 H), 3.75 - (M+H)+
195 ylc arbonyl) amino] be 3.90 (m, 1 H), 4.21 (d, 7=13.4 Hz, 1 H), 4.85
nzoyl}piperidin-4- (s, 4 H), 6.59 (d, 7=6.1 Hz, 1 H), 7.10 - 7.25 yl)carbamate (m, 5 H), 7.45 - 7.55 (m, 4 H), 7.89 (d, 7=8.5
Hz, 2 H), 8.26 (s, 1 H) 8.64 (s, 1 H)
N-(4-{ [3- ¾ NMR (400 MHz, DMSO-^ Deuterium (ESI(+))
(morpholin-4- Oxide, Temp=90°C) δ ppm 7.75-7.78 (m, m/e 409 yl)propyl] carbamoyl 2H), 7.63-7.66 (m, 2H), 7.26-7.42 (m, 4H), (M+H)+
196 }phenyl)-l,3- 4.79 (s, 4H), 3.82-3.86 (m, 4H), 3.37 (t, 7 =
dihydro-2H- 6.6 Hz, 2H), 3.20-3.26 (m, 4H), 3.12-3.18
isoindole-2- (m, 2H), 1.89-2.03 (m, 2H)
carboxamide
N-[4-({4-[3-chloro- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.57- (ESI(+)) 5- 8.59 (m, IH), 8.55-8.57 (bs, IH), 8.23 (d, 7 = m/e 530
(trifluoromethyl)pyri 2.2 Hz, IH), 7.65-7.69 (m, 2H), 7.37-7.41 (M+H)+ din-2-yl]piperazin- 1 -
197 (m, 2H), 7.29-7.38 (m, 4H), 4.79-4.80 (bs,
yl } carbonyl)phenyl] - 4H), 3.59-3.84 (m, 4H), 3.45-3.58 (m, 4H) l,3-dihydro-2H- isoindole-2- carboxamide
N-(4-{ [4- ¾ NMR (400 MHz, Pyridine-^, (ESI(-))
(cyclohexylmethyl)pi Temp=90°C) δ ppm 8.31-8.33 (bs, IH), 7.91- m/e 445 perazin- 7.95 (m, 2H), 7.50-7.57 (m, 2H), 7.20-7.23 (M-H)"
1 yl] carbonyl } phenyl) (m, 2H), 7.15-7.19 (m, 2H), 4.86 (s, 4H),
198
-l,3-dihydro-2H- 3.63-3.74 (m, 4H), 2.40-2.43 (m, 4H), 2.16 isoindole-2- (d, 7 = 7.0 Hz, 2H), 1.75-1.81 (m, 2H), 1.56- carboxamide 1.70 (m, 3H), 1.43-1.56 (m, IH), 1.09-1.29
(m, 3H), 0.82-0.97 (m, 2H)
N-(4-{ [l-(3- ¾ NMR (300 MHz, DMSO-<¾ δ ppm 10.28 (ESI(-)) chlorobenzyl)- 1 H- (s, IH), 8.64 (s, IH), 8.18 (s, IH), 7.85-7.89 m/e 470 pyrazol-4- (m, 2H), 7.70-7.74 (m, 2H), 7.63 (s, IH), (M-H)"
199 yl]carbamoyl}phenyl 7.28-7.42 (m, 7H), 7.18-7.23 (m, IH), 5.33- )-l,3-dihydro-2H- 5.34 (bs, 2H), 4.79-4.81 (bs, 4H)
isoindole-2- carboxamide
N-(4-{ [3- ¾ NMR (400 MHz, Pyridine-^, (ESI(-))
(diethylcarb amoyl)pi Temp=90°C) δ ppm 8.27-8.29 (bs, IH), 7.89- m/e 447 peridin-1- 7.92 (m, 2H), 7.52-7.56 (m, 2H), 7.19-7.24 (M-H)" yl] carbonyl jphenyl)- (m, 2H), 7.15-7.19 (m, 2H), 4.85 (s, 4H),
200 l,3-dihydro-2H- 4.17-4.21 (m, IH), 3.19-3.43 (m, 5H), 2.94
isoindole-2- (ddd, 7 = 13.0, 12.1, 3.3 Hz, OH), 2.84 (tt, 7
carboxamide = 10.6, 4.1 Hz, IH), 1.89-2.07 (m, 2H), 1.58- 1.66 (m, IH), 1.43-1.58 (m, IH), 1.04 (t, 7 =
7.1 Hz, 6H)
N-(4-{ [3-(piperidin- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) 1- Temp=90°C) δ ppm 8.45-8.51 (m, IH), 8.32- m/e 407
201
yl)propyl] carbamoyl 8.36 (bs, IH), 8.16-8.18 (m, 2H), 7.93-7.96 (M+H)+ }phenyl)-l,3- (m, 2H), 7.19-7.24 (m, 2H), 7.15-7.19 (m,
Figure imgf000666_0001
eny 1] - 1 , 3 -dihy dro - 2H), 7.62-7.65 (m, 2H), 7.32-7.40 (m, 4H), (M+H)+
2H-isoindole-2- 4.82 (s, 4H), 3.22-3.30 (m, 2H), 1.53-1.63
carboxamide (m, 2H), 0.93 (t, J = 7.4 Hz, 3H)
N-(4- { [(2S)-l- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) hydroxybutan-2- Temp=90°C) δ ppm 8.28-8.29 (bs, 1H), 8.06- m/e 354 yl]carbamoyl}phenyl 8.08 (m, 2H), 7.87-7.90 (m, 2H), 7.57-7.61 (M+H)+
210 )-l,3-dihydro-2H- (m, 1H), 7.19-7.23 (m, 2H), 7.15-7.19 (m,
isoindole-2- 2H), 4.84 (s, 4H), 4.37-4.47 (m, 1H), 3.91 - carboxamide 3.99 (m, 2H), 1.84-1.96 (m, 1H), 1.71-1.85
(m, 1H), 1.03 (t, 7 = 7.5 Hz, 3H)
N-{4-[(5- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) fluoropyridin-2- Temp=90°C) δ ppm 10.45-10.47 (bs, 1H), m/e 377 yl)carbamoyl]phenyl 8.58 (dd, 7 = 9.1, 4.2 Hz, 1H), 8.42-8.44 (bs, (M+H)+
211 }-l,3-dihydro-2H- 1H), 8.24 (d, 7 = 3.0 Hz, 1H), 8.18-8.20 (m,
isoindole-2- 2H), 7.98-8.00 (m, 2H), 7.45 (ddd, 7 = 9.0, carboxamide 8.1, 3.1 Hz, 1H), 7.20-7.24 (m, 2H), 7.15- 7.20 (m, 2H), 4.86 (s, 4H)
N-{4- ¾ NMR (400 MHz, Pyridine-^, (ESI(+))
[(cyclopropylmethyl) Temp=90°C) δ ppm 8.23-8.24 (bs, 1H), 7.90- m/e 378 (propyl)carb amoyl] p 7.92 (m, 2H), 7.48-7.52 (m, 2H), 7.19-7.24 (M+H)+ henyl } - 1 ,3-dihydro- (m, 2H), 7.15-7.19 (m, 2H), 4.85 (s, 4H),
212
2H-isoindole-2- 3.49-3.53 (m, 2H), 3.35 (d, 7 = 6.7 Hz, 2H), carboxamide 1.58-1.66 (m, 2H), 0.96-1.07 (m, 1H), 0.81
(t, J = 7.4 Hz, 3H), 0.42-0.47 (m, 2H), 0.15- 0.19 (m, 2H)
N-(4- { [(2S)-l- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) methoxypropan-2- Temp=90°C) δ ppm 8.28-8.34 (m, 1H), 8.05- m/e 354 yl]carbamoyl}phenyl 8.08 (m, 2H), 7.88-7.90 (m, 2H), 7.54-7.63 (M+H)+
)-l,3-dihydro-2H- (m, 1H), 7.18-7.24 (m, 2H), 7.15-7.18 (m,
213
isoindole-2- 2H), 4.83 (s, 4H), 4.54-4.64 (m, 1H), 3.53
carboxamide (dd, J = 9.5, 5.2 Hz, 1H), 3.45 (dd, J = 9.5,
5.5 Hz, 1H), 3.27 (s, 3H), 1.30 (d, 7 = 6.8
Hz, 3H)
N-[4-(l,3,4,9- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) tetrahydro-2H-beta- Temp=90°C) δ ppm 11.10-11.13 (bs, 1H), m/e 437 carbolin-2- 8.29-8.30 (bs, 1H), 7.91-7.94 (m, 2H), 7.57- (M+H)+
214 ylcarbonyl)phenyl] - 7.61 (m, 2H), 7.57-7.60 (m, 1H), 7.45-7.48
l,3-dihydro-2H- (m, 1H), 7.16-7.25 (m, 6H), 4.96-4.97 (bs, isoindole-2- 2H), 4.87 (s, 4H), 3.86-3.92 (m, 2H), 2.85 (t, carboxamide 7 = 5.7 Hz, 2H)
N-[4-(tert- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) butylcarbamoyl)phen Temp=90°C) δ ppm 8.24-8.26 (bs, 1H), 7.96- m/e 338
215 yl]-l,3-dihydro-2H- 7.99 (m, 2H), 7.85-7.88 (m, 2H), 7.19-7.23 (M+H)+ isoindole-2- (m, 2H), 7.14-7.19 (m, 2H), 6.93-6.96 (bs, carboxamide 1H), 4.83 (s, 4H), 1.52 (s, 9H)
N-[4-({4-[4- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+))
(trifluoromethyl)phe Oxide) δ ppm 7.64-7.67 (m, 2H), 7.53-7.55 m/e 495 nyl]piperazin-l- (m, 2H), 7.36-7.42 (m, 4H), 7.31-7.36 (m, (M+H)+
216 yl } carbonyl)phenyl] - 2H), 7.09-7.11 (m, 2H), 4.79-4.80 (bs, 4H),
l,3-dihydro-2H- 3.55-3.76 (m, 4H), 3.26-3.43 (m, 4H)
isoindole-2- carboxamide
N-{4-[(3- ¾ NMR (400 MHz, Pyridine-^, (ESI(+))
217
methylbutan-2- Temp=90°C) δ ppm 8.28-8.29 (bs, 1H), 8.06- m/e 352
Figure imgf000668_0001
Figure imgf000669_0001
Figure imgf000670_0001
Figure imgf000671_0001
isoindole-2- 4.09-4.19 (m, 2H), 2.88 (ddd, 7 = 13.1, 11.1, carboxamide 3.2 Hz, IH), 2.57 (dd, 7 = 12.9, 10.1 Hz,
IH), 1.63-1.69 (m, IH), 1.47-1.61 (m, 2H),
I.34-1.45 (m, IH), 1.03 (dddd, 7 = 13.0,
I I.3, 10.6, 4.4 Hz, IH), 0.75 (d, 7 = 6.6 Hz,
3H)
N-(4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.56 (ESI(+)) carbamoylphenyl)- (s, IH), 7.76-7.83 (m, 2H), 7.73-7.85 (bs, m/e 282
250 l,3-dihydro-2H- IH), 7.63-7.67 (m, 2H), 7.30-7.39 (m, 4H), (M+H)+ isoindole-2- 7.09-7.19 (bs, IH), 4.79 (s, 4H)
carboxamide
N-(4-{ [(2S)-2- ¾ NMR (400 MHz, Pyridine-^, (ESI(-))
(trifluoromethyl)pyrr Temp=90°C) δ ppm 8.34-8.36 (bs, IH), 7.91- m/e 402 olidin-1- 7.93 (m, 2H), 7.65-7.68 (m, 2H), 7.20-7.25 (M-H)"
251 yl] carbonyl jphenyl)- (m, 2H), 7.15-7.19 (m, 2H), 5.25-5.34 (m,
l,3-dihydro-2H- IH), 4.85 (s, 4H), 3.50-3.56 (m, 2H), 1.95- isoindole-2- 2.02 (m, 2H), 1.80-1.89 (m, IH), 1.58-1.70 carboxamide (m, IH)
N-(4-{ [(2S)-l- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) hydroxy-4- Temp=90°C) δ ppm 8.29-8.30 (bs, IH), 8.06- m/e 382 methylpentan-2- 8.11 (m, 2H), 7.88-7.90 (m, 2H), 7.62 (d, 7 = (M+H)+ yl]carbamoyl}phenyl 8.0 Hz, IH), 7.19-7.24 (m, 2H), 7.14-7.18
252 )-l,3-dihydro-2H- (m, 2H), 4.84 (s, 4H), 4.58-4.67 (m, IH),
isoindole-2- 3.95 (d, 7 = 4.9 Hz, 3H), 1.82-1.93 (m, IH), carboxamide 1.73 (ddd, 7 = 14.0, 8.6, 5.5 Hz, IH), 1.68
(ddd, 7 = 13.7, 8.2, 5.5 Hz, IH), 0.99 (d, 7 =
6.6 Hz, 3H), 0.93 (d, 7 = 6.6 Hz, 3H)
N-(4-{ [(lR)-2- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) hydroxy-1- Temp=90°C) δ ppm 8.29-8.30 (bs, IH), 8.15- m/e 402 phenylethyl] c arb amo 8.18 (m, IH), 8.08-8.11 (m, 2H), 7.87-7.90 (M+H)+
253 yl } phenyl) -1,3 - (m, 2H), 7.61-7.64 (m, 2H), 7.27-7.33 (m,
dihydro-2H- 2H), 7.19-7.24 (m, 3H), 7.15-7.19 (m, 2H), isoindole-2- 5.68-5.73 (m, IH), 4.83 (s, 4H), 4.23 (d, 7 =
carboxamide 5.6 Hz, 2H)
N-{4-[(2- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) methylpyrrolidin- 1 - Temp=90°C) δ ppm 8.26-8.28 (bs, IH), 7.89- m/e 350 yl)carbonyl]phenyl } - 7.92 (m, 2H), 7.60-7.65 (m, 2H), 7.20-7.24 (M+H)+ l,3-dihydro-2H- (m, 2H), 7.15-7.19 (m, 2H), 4.86 (s, 4H),
254 isoindole-2- 4.26-4.36 (m, IH), 3.47 (t, 7 = 6.8 Hz, 2H),
carboxamide 1.92 (dq, 7 = 12.2, 7.1 Hz, IH), 1.67-1.78
(m, IH), 1.52-1.63 (m, IH), 1.41 (dtd, 7 =
12.2, 6.9, 5.2 Hz, IH), 1.22 (d, 7 = 6.2 Hz,
3H)
N-{4-[ethyl(2- ¾ NMR (400 MHz, Pyridine-^, (ESI(+)) methoxyethyl)carba Temp=90°C) δ ppm 8.24-8.26 (bs, IH), 7.89- m/e 368 moyl] phenyl } - 1 , 3 - 7.91 (m, 2H), 7.49-7.53 (m, 2H), 7.19-7.24 (M+H)+
255 dihydro-2H- (m, 2H), 7.15-7.19 (m, 2H), 4.85 (s, 4H),
isoindole-2- 3.62-3.66 (m, 2H), 3.53-3.58 (m, 2H), 3.50 carboxamide (q, 7 = 7.1 Hz, 2H), 3.24 (s, 3H), 1.11 (t, 7 =
7.1 Hz, 3H)
N-(4-{ [(2R)-l- ¾ NMR (400 MHz, Pyridine-^, Temp=90 (ESI(+)) hydroxy-3- C) δ ppm 8.29-8.30 (bs, IH), 8.05-8.08 (m, m/e 368
256
methylbutan-2- 2H), 7.87-7.90 (m, 2H), 7.46-7.53 (m, IH), (M+H)+ yl]carbamoyl}phenyl 7.19-7.24 (m, 2H), 7.15-7.19 (m, 2H), 4.84
Figure imgf000673_0001
dihydro-2H- (m, 2H), 7.15-7.18 (m, 2H), 4.85 (s, 4H),
isoindole-2- 4.27 (p, J = 6.7 Hz, 1H), 3.36 (q, 7 = 7.0 Hz, carboxamide 2H), 1.18 (1, 7 = 6.9 Hz, 3H), 1.11 (d, 7 = 6.7
Hz, 6H)
N-{4-[(3- ¾ NMR (500 MHz, DMSO-^ Deuterium (APCI(+) fluoropyrrolidin- 1 - Oxide) δ ppm 7.63-7.66 (m, 2H), 7.36-7.41 ) m/e 354 yl)carbonyl]phenyl } - (m, 2H), 7.33-7.36 (m, 2H), 7.31-7.35 (m, (M+H)+
265
l,3-dihydro-2H- 2H), 5.21-5.48 (m, 1H), 4.79 (s, 4H), 3.53- isoindole-2- 3.79 (m, 4H), 1.98-2.25 (m, 2H)
carboxamide
N-{4-[(l,3-dihydro- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+))
2H-isoindol-2- Oxide) δ ppm 7.59-7.62 (m, 2H), 7.37-7.40 m/e 396
266 ylc arbonyl) amino] be (m, 2H), 7.31-7.36 (m, 2H), 7.24-7.27 (m, (M+H)+ nzoyl } -N-isopropyl- 2H), 4.78-4.79 (bs, 4H), 1.00-1.27 (m, 6H)
beta-alanine
N-{4- ¾ NMR (400 MHz, DMSO- , (ESI(+))
[methyl(propyl)carba Temp=90°C) δ ppm 0.82 (t, 7=7.32 Hz, 3 H), m/e 338 moyl] phenyl } - 1 , 3 - 1.49 - 1.62 (m, 2 H), 2.92 (s, 3 H), 3.27 - (M+H)+
267
dihydro-2H- 3.34 (m, 2 H), 4.78 (s, 4 H), 7.23 - 7.37 (m, 6 isoindole-2- H), 7.58 - 7.63 (m, 2 H), 8.26 (s, 1 H)
carboxamide
5 ,6 -dimethoxy-N- { 4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.54 (ESI(+)) [(3- (s, 1H), 8.29 (t, 7 = 5.6 Hz, 1H), 7.75-7.78 m/e 460 phenylpropyl)carbam (m, 2H), 7.61-7.68 (m, 2H), 7.15-7.32 (m, (M+H)+
268 oyl]phenyl}-l,3- 5H), 6.95 (s, 2H), 4.69-4.70 (bs, 4H), 3.32 (s,
dihydro-2H- 6H), 3.21-3.30 (m, 2H), 2.59-2.68 (m, 2H),
isoindole-2- 1.76-1.90 (m, 2H)
carboxamide
N-(4-{ [3-(4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.57 (ESI(+)) chlorophenoxy)propy (s, 1H), 8.36 (t, 7 = 5.6 Hz, 1H), 7.75-7.79 m/e 450
1] carbamoyl } phenyl) (m, 2H), 7.64-7.68 (m, 2H), 7.29-7.39 (m, (M+H)+
269
-l,3-dihydro-2H- 6H), 6.94-6.98 (m, 2H), 4.79 (s, 4H), 4.03 (t, isoindole-2- 7 = 6.1 Hz, 2H), 3.37-3.44 (m, 2H), 1.97 (p, carboxamide 7 = 6.5 Hz, 2H)
N-(4-{ [4- ¾ NMR (500 MHz, DMSO-^ Deuterium (ESI(+))
(trifluoromethoxy)ph Oxide) δ ppm 7.89-7.93 (m, 2H), 7.85-7.89 m/e 442 enyl]carbamoyl }phe (m, 2H), 7.72-7.75 (m, 2H), 7.33-7.41 (m, (M+H)+
270
nyl)-l,3-dihydro-2H- 6H), 4.80-4.82 (bs, 4H)
isoindole-2- carboxamide
N-{4-[(4-phenyl-l,3- ¾ NMR (400 MHz, DMSO-^ Deuterium (ESI(+)) thiazol-2- Oxide, Temp=90°C) δ ppm 8.06-8.09 (m, m/e 441 yl)carbamoyl]phenyl 2H), 7.94-7.97 (m, 2H), 7.75-7.78 (m, 2H), (M+H)+
271
}-l,3-dihydro-2H- 7.55 (s, 1H), 7.44-7.49 (m, 2H), 7.37-7.41
isoindole-2- (m, 2H), 7.32-7.37 (m, 3H), 4.84 (s, 4H)
carboxamide
5-bromo-N-[4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.60 (ESI(+)) (propylcarbamoyl)ph (s, 1H), 8.25 (t, 7 = 5.6 Hz, 1H), 7.74-7.78 m/e 402 eny 1] - 1 , 3 -dihy dro - (m, 2H), 7.62-7.67 (m, 2H), 7.59-7.62 (m, (M+H)+
284 2H-isoindole-2- 1H), 7.50 (dd, 7 = 8.1, 1.9 Hz, 1H), 7.34 (d, 7
carboxamide = 8.1 Hz, 1H), 4.70-4.82 (m, 4H), 3.15-3.26
(m, 2H), 1.45-1.61 (m, 2H), 0.89 (t, 7 = 7.4
Hz, 3H)
373 5-fluoro-N-[4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.58 (ESI(+))
Figure imgf000675_0001
carboxamide H), 8.58 (s, 1 H)
Figure imgf000676_0001
Figure imgf000677_0001
y p eny - , - , . - . m, , . - . m, dihydro-2H- 3H), 5.12 - 5.01 (m, IH), 4.90 (t, J = 5.8 Hz, isoindole-2- IH), 4.81 - 4.73 (m, 4H), 3.78 - 3.59 (m,
carboxamide 2H)
5-fluoro-N-(4- ¾ NMR (300 MHz, DMSO-d6) δ 8.62 (s, (ESI(+))
{ [(lS)-2-hydroxy-l- IH), 8.53 (ddd, 7 = 4.8, 1.8, 0.9 Hz, IH), m/e 421
(pyridin-2- 8.46 (d, 7 = 7.8 Hz, IH), 7.90 - 7.82 (m, (M+H)+ yl)ethyl]carbamoyl}p 2H), 7.78 - 7.71 (m, IH), 7.69 (t, 7 = 5.5 Hz,
571
henyl) - 1 , 3 - dihydro - 2H), 7.44 - 7.36 (m, 2H), 7.30 - 7.09 (m,
2H-isoindole-2- 3H), 5.19 - 5.08 (m, IH), 4.90 (t, 7 = 5.9 Hz, carboxamide IH), 4.87 - 4.72 (m, 4H), 3.89 - 3.72 (m,
2H); )
5-fluoro-N-(4- ¾ NMR (300 MHz, DMSO-d6) δ 8.59 (s, (ESI(+))
{ [(2S)-l-hydroxy-4- IH), 7.84 - 7.75 (m, 3H), 7.68 - 7.61 (m, m/e 400 methylpentan-2- 2H), 7.40 (dd, 7 = 8.4, 5.2 Hz, IH), 7.24 (dd, (M+H)+ yl]carbamoyl}phenyl 7 = 9.1, 2.5 Hz, IH), 7.15 (td, 7 = 8.9, 2.5
572
)-l,3-dihydro-2H- Hz, IH), 4.80 - 4.73 (m, 4H), 4.65 (t, 7 = 5.7 isoindole-2- Hz, IH), 4.10 - 3.97 (m, IH), 3.49 - 3.35
carboxamide (m, IH), 1.74 - 1.54 (m, IH), 1.52 - 1.31 (m,
2H), 0.88 (t, 7 = 6.8 Hz, 6H)
N-(4-{ [(2S)-l- ¾ NMR (400 MHz, DMSO-<¾ δ ppm 8.58 (ESI(+)) hydroxy-4- (s, IH), 7.90 (d, 7 = 8.3 Hz, IH), 7.79 (m, m/e 400
(methylthio)butan-2- 2H), 7.67 (m, 2H), 7.40 - 7.29 (m, 4H), 4.79 (M+H)+
585 yl]carbamoyl}phenyl (s, 4H), 4.73 (m, IH), 4.03 (m, IH), 3.47 (m,
)-l,3-dihydro-2H- IH), 3.58 (m, IH), 2.60 - 2.40 (m, 2H), 2.04 isoindole-2- (s, 3H), 1.90 (m, IH), 1.74 (m, IH)
carboxamide
N-(4-{ [(2S,3S)-l- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.57 (ESI(+)) hydroxy-3- (s, IH), 7.80 (m, 3H), 7.66 (m, 2H), 7.34 (m, m/e 382 methylpentan-2- 4H), 4.79 (bs, 4H), 4.52 (t, 7 = 5.5 Hz, IH), (M+H)+
586 yl]carbamoyl}phenyl 3.84 (m, IH), 3.53 (m, 2H), 1.69 (m, IH),
)-l,3-dihydro-2H- 1.49 (m, IH), 1.10 (m, IH), 0.91 - 0.81 (m, isoindole-2- 6H)
carboxamide
N-(4-{ [(2S)-l- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.57 (ESI(+)) hydroxyprop an -2 - (s, IH), 7.89 (d, 7 = 8.0 Hz, IH), 7.78 (m, m/e 340 yl]carbamoyl}phenyl 2H), 7.66 (m, 2H), 7.40 - 7.29 (m, 4H), 4.79 (M+H)+
587
)-l,3-dihydro-2H- (bs, 4H), 4.70 (t, 7 = 5.7 Hz, IH), 4.00 (m, isoindole-2- IH), 3.46 (dt, 7 = 10.8, 3.33 (m, IH), 5.4 Hz, carboxamide IH), 1.13 (d, 7 = 6.7 Hz, 3H)
N-(4-{ [(2S,3R)-l,3- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.57 (ESI(+)) dihydroxybutan-2- (bs, IH), 7.78 (m, 3H), 7.67 (m, 2H), 7.40 - m/e 370 yl]carbamoyl}phenyl 7.29 (m, 4H), 4.79 (bs, 4H), 4.67 (d, 7 = 5.2 (M+H)+
588
)-l,3-dihydro-2H- Hz, IH), 4.52 (m, IH), 3.90 - 3.72 (m, 2H), isoindole-2- 3.63 (m, 2H), 1.08 (d, 7 = 6.12 Hz, 3H)
carboxamide
N-(4-{ [(2S)-l- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.57 (ESI(+)) hydroxyhexan-2- (s, IH), 7.80 (m, 3H), 7.66 (m, 2H), 7.40 - m/e 382 yl]carbamoyl}phenyl 7.29 (m, 4H), 4.79 (bs, 4H), 4.65 (t, 7 = 5.7 (M+H)+
589 )-l,3-dihydro-2H- Hz, IH), 3.93 (m, IH), 3.44 (dt, 7 = 10.8, 5.4
isoindole-2- Hz, IH), 3.32 (m, IH), 1.63 (m, IH), 1.44
carboxamide (m, IH), 1.28 (m, 4H), 0.86 (t, 7 = 6.3 Hz,
3H)
Figure imgf000679_0001
Ν-(4-{ [(1- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, (ESI(+)) methylpyrrolidin-3 - IH), 8.40 (t, J = 5.7 Hz, IH), 7.81 - 7.73 (m, m/e 379 yl)methyl]carbamoyl 2H), 7.71 - 7.63 (m, 2H), 7.41 - 7.28 (m, (M+H)+
}phenyl)-l,3- 6H), 5.83 (dd, 7 = 19.3, 15.2 Hz, IH), 4.79
716
dihydro-2H- (bs, 4H), 3.30 - 3.21 (m, IH), 3.06 - 2.93
isoindole-2- (m, IH), 2.89 - 2.69 (m, IH), 2.60 (dd, 7 =
carboxamide 17.2, 7.4 Hz, IH), 2.32 (s, 3H), 2.04 - 1.85
(m, IH), 1.58 (tt, 7 = 13.9, 6.9 Hz, IH)
N-(4-{ [(l- ¾ NMR (300 MHz, DMSO-d6) δ 8.57 (s, (ESI(+)) methylpiperidin-4- IH), 8.27 (t, J = 5.8 Hz, IH), 7.80 - 7.73 (m, m/e 393 yl)methyl]carbamoyl 2H), 7.69 - 7.62 (m, 2H), 7.41 - 7.28 (m, (M+H)+
}phenyl)-l,3- 4H), 3.35 - 3.27 (m, 2H), 3.13 (t, J = 6.2 Hz,
719
dihydro-2H- 2H), 3.03 - 2.93 (m, IH), 2.86 - 2.77 (m,
isoindole-2- 2H), 2.20 (s, 3H), 2.17 (s, IH), 2.00 - 1.82
carboxamide (m, 2H), 1.70 - 1.45 (m, 3H), 1.28 - 1.11 (m,
2H)
N-(4-{ [(l,l- ¾ NMR (300 MHz, DMSO DMSO-d6) δ (ESI(+)) dioxidotetrahydrothi 8.58 (s, IH), 8.44 (t, 7 = 5.8 Hz, 1H), 7.81 - m/e 414 ophen-3- 7.74 (m, 2H), 7.71 - 7.64 (m, 2H), 7.41 - (M+H)+ yl)methyl]carbamoyl 7.28 (m, 4H), 4.79 (s, 4H), 3.41 - 3.31 (m,
781
}phenyl)-l,3- 2H), 3.30 (s, 2H), 3.11 - 2.81 (m, 2H), 2.74 dihydro-2H- - 2.59 (m, IH), 2.30 - 2.15 (m, IH), 1.94 - isoindole-2- 1.76 (m, IH)
carboxamide
N-(4-{ [(2,2- ¾ NMR (300 MHz, DMSO-d6) δ 8.58 (s, (ESI(+)) dimethyl-1,3- IH), 8.38 (t, 7 = 5.8 Hz, IH), 8.01 - 7.89 (m, m/e 396 dioxolan-4- IH), 7.78 (d, J = 8.9 Hz, 2H), 7.67 (d, J = (M+H)+ yl)methyl]carbamoyl 8.8 Hz, 2H), 7.44 - 7.24 (m, 4H), 4.79 (s,
782
}phenyl)-l,3- 4H), 4.20 (p, 7 = 5.9 Hz, IH), 3.98 (dd, 7 =
dihydro-2H- 8.3, 6.2 Hz, IH), 3.71 (dd, 7 = 8.3, 5.8 Hz, isoindole-2- IH), 3.50 - 3.20 (m, IH), 1.35 (s, 3H), 1.26 carboxamide (s, 3H)
N-(4-{ [(lS)-2- ¾ NMR (300 MHz, DMSO-d6) δ 8.61 (d, 7 (ESI(+)) methoxy-1- = 8.2 Hz, 2H), 7.87 - 7.79 (m, 2H), 7.70 (s, m/e 416 phenylethyl] c arb amo IH), 7.67 (s, IH), 7.46 - 7.20 (m, 9H), 5.27 (M+H)+
783 yl } phenyl) -1,3 - (td, 7 = 8.4, 5.4 Hz, IH), 4.79 (s, 4H), 3.70
dihydro-2H- (dd, 7 = 10.0, 8.6 Hz, IH), 3.55 (dd, 7 = 10.0, isoindole-2- 5.5 Hz, IH), 3.30 (d, 7 = 2.9 Hz, 3H)
carboxamide
N-[4-({ [(4S)-2,2- ¾ NMR (300 MHz, DMSO-d6) δ 8.58 (s, (ESI(+)) dimethyl-1,3- IH), 8.39 (t, 7 = 5.8 Hz, IH), 7.81 - 7.74 (m, m/e 396 dioxolan-4- 2H), 7.70 - 7.63 (m, 2H), 7.41 - 7.28 (m, (M+H)+ yl] methyl } carbamoyl 4H), 4.79 (s, 4H), 4.20 (p, 7 = 5.9 Hz, IH),
784
)phenyl]-l,3- 3.98 (dd, 7 = 8.3, 6.2 Hz, IH), 3.71 (dd, 7 =
dihydro-2H- 8.3, 5.8 Hz, IH), 3.30 (s, IH), 1.35 (s, 3H), isoindole-2- 1.26 (s, 3H)
carboxamide
N-[4-({ [(4R)-2,2- ¾ NMR (300 MHz, DMSO-d6) δ 8.58 (s, (ESI(+)) dimethyl-1,3- IH), 8.39 (t, 7 = 5.8 Hz, IH), 7.81 - 7.74 (m, m/e 396 dioxolan-4- 2H), 7.70 - 7.63 (m, 2H), 7.43 - 7.27 (m, (M+H)+
785 yl] methyl } carbamoyl 4H), 4.79 (s, 4H), 4.20 (p, 7 = 5.9 Hz, IH),
)phenyl]-l,3- 3.98 (dd, 7 = 8.3, 6.2 Hz, IH), 3.71 (dd, 7 =
dihydro-2H- 8.3, 5.8 Hz, IH), 3.38 (ddd, 7 = 14.9, 12.8, isoindole-2- 5.8 Hz, IH), 1.35 (s, 3H), 1.26 (s, 3H)
Figure imgf000681_0001
isoindole-2- 3.93 - 4.02 (m, 1 H) 3.59 - 3.84 (m, 1 H)
carboxamide 3.58 (d, 7=5.80 Hz, 2 H)
5-cyano-N-(4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) { [(2R)-2- Temp=90°C) δ ppm 7.68 - 7.84 (m, 4 H) m/e 365 hydroxypropyl] carba 7.54 - 7.64 (m, 3 H) 4.85 (d, 7=8.24 Hz, 4 H) (M+H)+
814 moyl } phenyl) -1,3- 3.77 - 3.88 (m, 1 H) 3.15 - 3.26 (m, 2 H)
dihydro-2H- 1.10 (d, 7=6.10 Hz, 3 H)
isoindole-2- carboxamide
5-cyano-N-{4-[(2- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) hydroxy-2- Temp=90°C) δ ppm 7.69 - 7.81 (m, 4 H) m/e 379 methylpropyl)carbam 7.54 - 7.65 (m, 3 H) 4.85 (d, 7=8.24 Hz, 4 H) (M+H)+
815 oyl]phenyl}-l,3- 3.28 (s, 2 H) 1.14 (s, 6 H)
dihydro-2H- isoindole-2- carboxamide
5-cyano-N-(4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+))
{ [(2R)-l-hydroxy-3- Temp=90°C) δ ppm 7.69 - 7.81 (m, 4 H) m/e 393 methylbutan-2- 7.55 - 7.64 (m, 3 H) 4.85 (d, 7=8.24 Hz, 4 H) (M+H)+
816 yl]carbamoyl}phenyl 3.76 - 3.84 (m, 1 H) 3.56 (d, 7=5.19 Hz, 2 H)
)-l,3-dihydro-2H- 1.87 - 2.00 (m, 1 H) 0.92 (dd, 7=11.75, 6.87 isoindole-2- Hz, 6 H)
carboxamide
5-cyano-N-(4-{ [(2S)- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) tetrahydrofuran-2 - Temp=90°C) δ ppm 7.69 - 7.81 (m, 4 H) m/e 391 ylmethyl]carbamoyl} 7.54 - 7.63 (m, 3 H) 4.85 (d, 7=8.24 Hz, 4 H) (M+H)+
817
phenyl)- 1 ,3-dihydro- 3.95 - 4.05 (m, 1 H) 3.75 - 3.84 (m, 1 H)
2H-isoindole-2- 3.60 - 3.68 (m, 1 H) 3.34 (d, 7=5.80 Hz, 2 H) carboxamide 1.75 - 1.98 (m, 3 H) 1.54 - 1.66 (m, 1 H)
5-cyano-N-(4-{ [2-(4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) methylpiperazin- 1 - Temp=90°C) δ ppm 7.70 - 7.81 (m, 4 H) m/e 433 yl)ethyl]carbamoyl}p 7.60 - 7.66 (m, 2 H) 7.57 (d, 7=7.93 Hz, 1 H) (M+H)+
818
henyl) - 1 , 3 - dihydro - 4.85 (d, 7=8.85 Hz, 4 H) 3.50 (t, 7=6.41 Hz,
2H-isoindole-2- 2 H) 3.22 - 3.26 (m, 4 H) 3.04 (d, 7=4.88 Hz, carboxamide 4 H) 2.90 (t, 7=6.41 Hz, 2 H) 2.78 (s, 3 H)
5-cyano-N-(4-{ [(lS)- ¾ NMR (400 MHz, DMSO-D20 Temp=90 (ESI(+))
2-hydroxy-l- °C) δ ppm 7.78 - 7.85 (m, 3 H) 7.70 - 7.74 m/e 427 phenylethyl] c arb amo (m, 1 H) 7.60 - 7.66 (m, 2 H) 7.56 (d, 7=8.24 (M+H)+
819 yl } phenyl) -1,3 - Hz, 1 H) 7.38 - 7.43 (m, 2 H) 7.28 - 7.34 (m,
dihydro-2H- 2 H) 7.19 - 7.26 (m, 1 H) 5.03 - 5.13 (m, 1
isoindole-2- H) 4.85 (d, 7=8.24 Hz, 4 H) 3.68 - 3.79 (m, 2 carboxamide H)
5-cyano-N-{4-[(4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) hydroxybutyl)carbam Temp=90°C) δ ppm 7.79 (s, 1 H) 7.70 - 7.76 m/e 377 oyl]phenyl}-l,3- (m, 3 H) 7.58 - 7.64 (m, 2 H) 7.56 (d, 7=8.24 (M+H)+
820
dihydro-2H- Hz, 1 H) 4.85 (d, 7=8.24 Hz, 4 H) 4.44 (t,
isoindole-2- 7=6.41 Hz, 1 H) 3.45 (t, 7=6.41 Hz, 1 H)
carboxamide 3.27 - 3.34 (m, 2 H) 1.46 - 1.81 (m, 4 H)
5-cyano-N-(4-{ [(2S)- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) 2- Temp=90°C) δ ppm 7.69 - 7.82 (m, 4 H) m/e 365
821 hydroxypropyl] carba 7.53 - 7.64 (m, 3 H) 4.85 (d, 7=8.24 Hz, 4 H) (M+H)+ moyl } phenyl) -1,3- 3.79 - 3.87 (m, 1 H) 3.17 - 3.26 (m, 2 H)
dihydro-2H- 1.10 (d, 7=6.10 Hz, 3 H) isoindole-2- carboxamide
5-cyano-N-{4-[(3- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) fury lmethyl)c arb amo Temp=90°C) δ ppm 7.79 (s, 1 H) 7.74 - 7.78 m/e 387 yl] phenyl} -1,3 - (m, 2 H) 7.72 (d, 7=7.93 Hz, 1 H) 7.59 - 7.65 (M+H)+
822
dihydro-2H- (m, 2 H) 7.54 - 7.58 (m, 1 H) 7.50 - 7.53 (m, isoindole-2- 1 H) 7.25 (d, 7=8.54 Hz, 1 H) 6.46 (s, 1 H) carboxamide 4.85 (d, 7=8.85 Hz, 4 H) 4.31 (s, 2 H)
5-cyano-N-{4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+))
[(tetrahydrofuran-2- Temp=90°C) δ ppm 7.70 - 7.81 (m, 4 H) m/e 391 ylmethyl)carbamoyl] 7.55 - 7.64 (m, 3 H) 4.85 (d, 7=8.24 Hz, 4 H) (M+H)+
823
phenyl } - 1 , 3 -dihydro - 3.95 - 4.04 (m, 1 H) 3.75 - 3.83 (m, 1 H)
2H-isoindole-2- 3.61 - 3.68 (m, 1 H) 3.34 (d, 7=5.80 Hz, 2 H) carboxamide 1.75 - 1.98 (m, 3 H) 1.54 - 1.65 (m, 1 H)
5-cyano-N-(4-{ [4-(2- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) furoyl)piperazin- 1 - Temp=90°C) δ ppm 7.79 (s, 1 H) 7.73 - 7.75 m/e 470 yl] carbonyl jphenyl)- (m, 1 H) 7.71 (d, 7=1.53 Hz, 1 H) 7.60 - 7.65 (M+H)+
824 l,3-dihydro-2H- (m, 2 H) 7.57 (d, 7=8.54 Hz, 1 H) 7.34 - 7.40
isoindole-2- (m, 2 H) 7.00 (d, 7=2.75 Hz, 1 H) 6.59 (dd, carboxamide 7=3.51, 1.68 Hz, 1 H) 4.85 (d, 7=8.54 Hz, 4
H) 3.71 - 3.77 (m, 4 H) 3.54 - 3.65 (m, 4 H)
5-cyano-N-(4-{ [4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) (tetrahydrofuran-2- Temp=90°C) δ ppm 7.79 (s, 1 H) 7.72 (dd, m/e 474 ylcarbonyl)piperazin- 7=7.93, 1.53 Hz, 1 H) 7.59 - 7.64 (m, 2 H) (M+H)+ 1- 7.57 (d, 7=7.93 Hz, 1 H) 7.33 - 7.37 (m, 2 H)
825
yl] carbonyl jphenyl)- 4.85 (d, 7=8.24 Hz, 4 H) 4.64 (dd, 7=7.48,
l,3-dihydro-2H- 5.95 Hz, 1 H) 3.71 - 3.86 (m, 2 H) 3.48 - isoindole-2- 3.61 (m, 8 H) 1.96 - 2.14 (m, 2 H) 1.75 - carboxamide 1.94 (m, 2 H)
5-cyano-N-(4-{ [3- ¾ NMR (400 MHz, DMSO-D20 (ESI(+))
(piperidin-1- Temp=90°C) δ ppm 7.70 - 7.81 (m, 4 H) m/e 432 yl)propyl] carbamoyl 7.61 - 7.66 (m, 2 H) 7.57 (d, 7=7.93 Hz, 1 H) (M+H)+
826 }phenyl)-l,3- 4.85 (d, 7=8.24 Hz, 4 H) 3.36 (t, 7=6.71 Hz,
dihydro-2H- 4 H) 3.02 - 3.13 (m, 2 H) 2.90 (s, 2 H) 1.90 - isoindole-2- 2.18 (m, 2 H) 1.81 (d, 7=84.53 Hz, 6 H)
carboxamide
5-cyano-N-(4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) { [(2R)- Temp=90°C) δ ppm 7.70 - 7.81 (m, 4 H) m/e 391 tetrahydrofuran-2 - 7.55 - 7.64 (m, 3 H) 4.85 (d, 7=8.54 Hz, 4 H) (M+H)+
827 ylmethyl]carbamoyl} 3.96 - 4.04 (m, 1 H) 3.76 - 3.85 (m, 1 H)
phenyl)- 1 ,3-dihydro- 3.61 - 3.68 (m, 1 H) 3.34 (d, 7=5.80 Hz, 2 H)
2H-isoindole-2- 1.75 - 1.98 (m, 3 H) 1.54 - 1.67 (m, 1 H)
carboxamide
5-cyano-N-(4-{ [4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+))
(ethylsulfonyl)pipera Temp=90°C) δ ppm 7.79 (s, 1 H) 7.72 (dd, m/e 468 zin-1- 7=7.93, 1.53 Hz, 1 H) 7.59 - 7.64 (m, 2 H) (M+H)+
828 yl] carbonyl jphenyl)- 7.57 (d, 7=7.63 Hz, 1 H) 7.32 - 7.37 (m, 2 H)
l,3-dihydro-2H- 4.85 (d, 7=8.24 Hz, 4 H) 3.56 - 3.61 (m, 4 H) isoindole-2- 3.27 (s, 4 H) 3.07 (q, 7=7.32 Hz, 2 H) 1.24
carboxamide (t, 7=7.32 Hz, 3 H)
5-cyano-N-{4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+))
829 [(tetrahydrofuran-3- Temp=90°C) δ ppm 7.79 (s, 1 H) 7.72 - 7.77 m/e 391 ylmethyl)carbamoyl] (m, 2 H) 7.71 (d, 7=1.22 Hz, 1 H) 7.59 - 7.64 (M+H)+
Figure imgf000684_0001
car oxam e (m, 2 H) 5-cyano-N-(4-{ [(l- ¾ NMR (400 MHz, DMSO-D20 (ESI(+)) methylpiperidin-4- Temp=90°C) δ ppm 7.67 - 7.83 (m, 4 H) m/e 418 yl)methyl]carbamoyl 7.54 - 7.65 (m, 3 H) 4.85 (d, 7=8.24 Hz, 4 H) (M+H)+
837 }phenyl)-l,3- 3.36 - 3.52 (m, 2 H) 3.18 - 3.25 (m, 2 H)
dihydro-2H- 2.92 (s, 2 H) 2.76 (s, 3 H) 1.89 (m, 3 H) 1.29 isoindole-2- - 1.54 (m, 2 H)
carboxamide
5-cyano-N-{4- ¾ NMR (400 MHz, DMSO-D20 (ESI(+))
[(tetrahydro-2H- Temp=90°C) δ ppm 7.68 - 7.82 (m, 4 H) m/e 405 pyran-3- 7.52 - 7.65 (m, 3 H) 4.85 (d, 7=8.54 Hz, 4 H) (M+H)+
838 ylmethyl)carbamoyl] 3.65 - 3.82 (m, 2 H) 3.29 - 3.40 (m, 1 H)
phenyl } - 1 , 3 -dihydro - 3.09 - 3.20 (m, 3 H) 1.73 - 1.92 (m, 2 H)
2H-isoindole-2- 1.40 - 1.69 (m, 2 H) 1.20 - 1.35 (m, 1 H)
carboxamide
N-{4-[(pyrrolidin-3- 1H NMR (300 MHz, DMSO-d6) δ 9.07 (bs, (ESI(+)) ylmethyl)carbamoyl] 1H), 8.64 (s, 1H), 8.51 (t, 7 = 5.8 Hz, 1H), m/e 340 phenyl } - 1 , 3 -dihydro - 7.83 - 7.75 (m, 1H), 7.73 - 7.65 (m, 2H), (M+H)+ 2H-isoindole-2- 7.42 - 7.28 (m, 3H), 4.86 (bs, 2H), 4.79 (s,
717
carboxamide 4H), 3.75 - 3.64 (m, 1H), 3.53 - 3.43 (m,
1H), 3.40 - 3.16 (m, 3H), 3.10 (dt, 7 = 13.6,
7.7 Hz, 1H), 2.98 - 2.83 (m, 1H), 2.07 - 1.92
(m, 1H), 1.84 - 1.46 (m, 1H)
N-[4-(2,6- ¾ NMR (400 MHz, DMSO-D20) δ 7.67 - (ESI(+)) diazaspiro [3.3]hept- 7.61 (m, 2H), 7.57 - 7.51 (m, 2H), 7.40 - m/e 363 2- 7.26 (m, 4H), 4.79 (s, 4H), 4.36 (bs, 4H), (M+H)+
840 ylcarbonyl)phenyl] - 4.20 (s, 4H)
l,3-dihydro-2H- isoindole-2- carboxamide
N-[4-(2,6- ¾ NMR (400 MHz, DMSO-D20) δ 7.70 - (ESI(+)) diazaspiro [3.4]oct-6- 7.56 (m, 2H), 7.48 - 7.42 (m, 2H), 7.38 - m/e 377 ylcarbonyl)phenyl] - 7.29 (m, 4H), 4.79 (s, 4H), 3.99 (q, 7 = 10.6 (M+H)+
841
l,3-dihydro-2H- Hz, 4H), 3.74 (s, 2H), 3.52 (t, 7 = 7.0 Hz,
isoindole-2- 2H), 2.18 (t, 7 = 7.1 Hz, 2H)
carboxamide
N-[4-(2,7- ¾ NMR (400 MHz, DMSO-D20) δ 7.73 - (ESI(+)) diazaspiro [3.5]non-7 - 7.53 (m, 2H), 7.42 - 7.31 (m, 4H), 7.31 - m/e 391 ylcarbonyl)phenyl] - 7.25 (m, 2H), 4.79 (s, 4H), 3.81 (d, 7 = 5.0 (M+H)+
842
l,3-dihydro-2H- Hz, 4H), 3.44 (dd, 7 = 12.2, 6.6 Hz, 4H),
isoindole-2- 1.92 - 1.53 (m, 4H)
carboxamide
N-[4-(2,6- ¾ NMR (400 MHz, DMSO-D20) δ 7.67 - (ESI(+)) diazaspiro [3.5]non-2- 7.61 (m, 2H), 7.58 - 7.54 (m, 2H), 7.39 - m/e 391 ylcarbonyl)phenyl] - 7.29 (m, 4H), 4.79 (s, 4H), 4.07 (d, 7 = 7.8 (M+H)+
843 l,3-dihydro-2H- Hz, 2H), 3.95 (d, 7 = 22.6 Hz, 2H), 2.99 (t, 7
isoindole-2- = 11.8, 6.0 Hz, 2H), 2.55 (s, 2H), 1.97 - 1.82 carboxamide (m, 2H), 1.82 - 1.59 (m, 2H)
N-[4-(l,7- ¾ NMR (400 MHz, DMSO-D20) δ 7.72 - (ESI(+)) diazaspiro [4.4]non- 1 - 7.57 (m, 2H), 7.50 - 7.40 (m, 2H), 7.40 - m/e 391 ylcarbonyl)phenyl] - 7.22 (m, 4H), 4.79 (s, 4H), 3.83 (d, 7 = 12.2 (M+H)+
844
l,3-dihydro-2H- Hz, 1H), 3.75 - 3.63 (m, 1H), 3.57 - 3.42
isoindole-2- (m, 2H), 3.17 (t, 7 = 13.0 Hz, 1H), 2.61 (m, 7 carboxamide = 13.5, 9.0 Hz, 1H), 2.27 - 1.99 (m, 3H),
Figure imgf000686_0001
l,3-dihydro-2H- 2H), 3.09 - 3.00 (m, 1H), 3.00 - 2.94 (m,
Figure imgf000687_0001
carboxamide 1H), 1.59- 1.38 (m, 1H) N-[4-(l,8- ¾ NMR (400 MHz, DMSO-D20) δ 7.71 - (ESI(+)) diazaspiro [4.5] dec- 1 - 7.48 (m, 2H), 7.45 - 7.18 (m, 6H), 4.79 (s, m/e 405 ylcarbonyl)phenyl] - 4H), 3.44 (t, 7 = 6.7 Hz, 2H), 3.36 (dd, 7 = (M+H)+
860
l,3-dihydro-2H- 7.3, 5.1 Hz, 1H), 3.24 - 3.06 (m, 2H), 3.05 - isoindole-2- 2.85 (m, 2H), 2.05 (t, 7 = 7.0 Hz, 2H), 1.88 - carboxamide 1.72 (m, 2H), 1.65 (dd, 7 = 12.7, 1.4 Hz, 2H)
N-[4-(l,8- ¾ NMR (400 MHz, DMSO-D20) δ 7.75 - (ESI(+)) diazaspiro [4.5] dec- 8 - 7.51 (m, 2H), 7.42 - 7.10 (m, 6H), 4.79 (s, m/e 405 ylcarbonyl)phenyl] - 4H), 3.92 - 3.68 (m, 2H), 3.36 (dd, 7 = 8.1, (M+H)+
861
l,3-dihydro-2H- 5.4 Hz, 1H), 3.31 - 3.21 (m, 2H), 2.14 - 1.91 isoindole-2- (m, 4H), 1.91 - 1.68 (m, 4H)
carboxamide
N-[4-(2,6- ¾ NMR (400 MHz, DMSO-D20) δ 7.72 - (ESI(+)) diazaspiro [3.4]oct-2- 7.60 (m, 2H), 7.60 - 7.49 (m, 2H), 7.42 - m/e 377 ylcarbonyl)phenyl] - 7.21 (m, 4H), 4.79 (s, 4H), 4.20 (dd, 7 = (M+H)+
862
l,3-dihydro-2H- 29.4, 9.1 Hz, 4H), 3.42 (s, 2H), 3.27 (d, 7 =
isoindole-2- 3.7 Hz, 1H), 3.24 (s, 1H), 2.24 (t, 7 = 7.4 Hz, carboxamide 2H)
N-[4-(l,7- ¾ NMR (400 MHz, DMSO-D20) δ 7.72 - (ESI(+)) diazaspiro [3.5]non-7 - 7.52 (m, 2H), 7.43 - 7.10 (m, 6H), 5.54 (s, m/e 390 ylcarbonyl)phenyl] - 1H), 4.79 (s, 4H), 3.99 (d, 7 = 11.5 Hz, 2H), (M+H)+
863
l,3-dihydro-2H- 3.68 - 3.49 (m, 2H), 2.95 (t, 7 = 7.4 Hz, 2H), isoindole-2- 2.53 - 2.51 (m, 1H), 2.41 - 2.25 (m, 2H),
carboxamide 2.07 (t, 7 = 31.9 Hz, 2H)
N-[4-(l,6- ¾ NMR (400 MHz, DMSO-D20) δ 7.75 - (ESI(+)) diazaspiro [3.5]non- 1 - 7.61 (m, 2H), 7.60 - 7.48 (m, 2H), 7.42 - m/e 391 ylcarbonyl)phenyl] - 7.12 (m, 4H), 4.79 (s, 4H), 4.54 - 4.29 (m, (M+H)+ l,3-dihydro-2H- 1H), 4.14 - 3.91 (m, 1H), 3.86 - 3.55 (m,
864
isoindole-2- 1H), 3.26 - 3.18 (m, 1H), 3.12 - 2.79 (m,
carboxamide 1H), 2.50 (dd, 7 = 9.4, 1.3 Hz, 1H), 2.43 - 2.20 (m, 1H), 2.17 - 2.01 (m, 1H), 2.01 - 1.85 (m, 2H), 1.87 - 1.52 (m, 1H)
N-[4-(2,5- ¾ NMR (400 MHz, DMSO-D20) δ 7.75 - (ESI(+)) diazaspiro [3.5]non-2- 7.62 (m, 2H), 7.62 - 7.52 (m, 2H), 7.44 - m/e 391 ylcarbonyl)phenyl] - 7.18 (m, 4H), 4.80 (s, 4H), 4.28 (d, 7 = 10.2 (M+H)+
865
l,3-dihydro-2H- Hz, 2H), 4.19 (s, 2H), 3.10 (t, 7 = 5.3 Hz,
isoindole-2- 2H), 2.01 (t, 7 = 5.4 Hz, 2H), 1.77 - 1.35 (m, carboxamide 4H)
N-[4-(5-oxa-2- ¾ NMR (400 MHz, DMSO-D20) δ 7.65 - (ESI(+)) azaspiro [3.4] oct-2- 7.60 (m, 2H), 7.57 - 7.53 (m, 2H), 7.40 - m/e 378 ylcarbonyl)phenyl] - 6.97 (m, 5H), 4.79 (s, 5H), 4.16 (dd, 7 = (M+H)+
866 l,3-dihydro-2H- 23.4, 9.6 Hz, 4H), 3.77 (t, 7 = 6.8 Hz, 2H),
isoindole-2- 3.35 (q, 7 = 7.1 Hz, 1H), 2.07 (dd, 7 = 8.1,
carboxamide 6.6 Hz, 2H), 1.98 - 1.74 (m, 2H), 1.11 (t, 7 =
7.1 Hz, 1H)
N-[4-(6-oxa-2- ¾ NMR (400 MHz, DMSO-D20) δ 7.65 - (ESI(+)) azaspiro[3.5]non-2- 7.60 (m, 2H), 7.58 - 7.54 (m, 2H), 7.38 - m/e 392 ylcarbonyl)phenyl] - 7.28 (m, 4H), 4.79 (s,4H), 3.95 - 3.67 (m, (M+H)+
867
l,3-dihydro-2H- 4H), 3.59 (s, 2H), 3.55 - 3.44 (m, 2H), 1.90 isoindole-2- - 1.72 (m, 2H), 1.61 - 1.39 (m, 2H)
carboxamide
N-[4-(hexahydro-5H- ¾ NMR (400 MHz, DMSO-D20) δ 7.75 - (ESI(+))
868 furo[2,3-c]pyrrol-5- 7.52 (m, 2H), 7.46 - 7.20 (m, 6H), 4.79 (s, m/e 378 ylcarbonyl)phenyl] - 4H), 4.49 - 4.27 (m, 1H), 3.95 - 3.78 (m, (M+H)+ l,3-dihydro-2H- 1H), 3.77 - 3.55 (m, 4H), 3.43 (dd, 7 = 11.8, isoindole-2- 5.4 Hz, 1H), 2.98 - 2.70 (m, 1H), 2.06 (ddd, carboxamide 7 = 15.0, 12.5, 7.7 Hz, 1H), 1.82 - 1.49 (m,
1H)
N-[4-(tetrahydro-lH- ¾ NMR (400 MHz, DMSO-D20) δ 7.69 - (ESI(+)) furo[3,4-c]pyrrol- 7.61 (m, 1H), 7.60 (d, 1H), 7.47 - 7.07 (m, m/e 378
5(3H)- 6H), 4.79 (s, 4H) , 3.83 - 3.59 (m, 4H), 3.58 (M+H)+
869 ylcarbonyl)phenyl] - - 3.33 (m, 4H), 3.05 - 2.82 (m, 2H)
l,3-dihydro-2H- isoindole-2- carboxamide
N-[4- ¾ NMR (400 MHz, DMSO-D20) δ 7.71 - (ESI(+))
(hexahydrofuro [3,4- 7.52 (m, 2H), 7.41 - 7.12 (m, 6H), 4.79 (s, m/e 392 c]pyridin-5(3H)- 4H), 3.89 - 3.65 (m,2H), 3.67 - 3.40 (m, (M+H)+
870 ylcarbonyl)phenyl] - 5H), 3.39 - 3.26 (m, 1H), 2.46 - 2.25 (m,
l,3-dihydro-2H- 2H), 1.88 - 1.63 (m, 1H), 1.67 - 1.24 (m,
isoindole-2- 1H)
carboxamide
N-[4-(2,6- ¾ NMR (400 MHz, DMSO-D20) δ 7.68 - (ESI(+)) diazaspiro [3.4]oct-6- 7.51 (m, 2H), 7.51 - 7.28 (m, 3H), 7.24 - m/e 393 ylcarbonyl)phenyl] - 7.00 (m, 1H), 4.77 (d, 7 = 12.1 Hz, 4H), 3.61 (M+H)+
885
5-fluoro-l,3-dihydro- (d, 7 = 17.1 Hz, 2H), 3.54 (d, 7 = 8.2 Hz,
2H-isoindole-2- 3H), 3.48 (t, 7 = 7.0 Hz, 2H), 2.06 (dd, 7 =
carboxamide 23.6, 16.6 Hz, 2H), 1.89 (s, 1H)
N-[4-(2,7- ¾ NMR (400 MHz, DMSO-D20) δ 7.65 - (ESI(+)) diazaspiro [3.5]non-7 - 7.53 (m, 2H), 7.37 (dd, 7 = 8.3, 5.2 Hz, 1H), m/e 407 ylcarbonyl)phenyl] - 7.31 - 7.22 (m, 2H), 7.17 (d, 7 = 9.0 Hz, (M+H)+
886
5-fluoro-l,3-dihydro- 1H), 7.15 - 6.92 (m, 1H), 4.77 (d, 7 = 12.3
2H-isoindole-2- Hz, 4H), 3.41 (t, 7 = 5.5 Hz, 8H), 1.78 - 1.63 carboxamide (m, 4H)
N-[4-(l,7- ¾ NMR (400 MHz, DMSO-D20) δ 7.65 - (ESI(+)) diazaspiro [4.4]non- 1 - 7.49 (m, 2H), 7.43 - 7.32 (m, 3H), 7.22 - m/e 409 ylcarbonyl)phenyl] - 7.03 (m, 2H), 4.76 (d, 7 = 12.6 Hz, 4H), 3.54 (M+H)+
887 5-fluoro-l,3-dihydro- - 3.37 (m, 2H), 2.86 (dt, 7 = 11.3, 7.9 Hz,
2H-isoindole-2- 1H), 2.70 (d, 7 = 11.7 Hz, 1H), 2.10 - 1.96
carboxamide (m, 1H), 1.90 (d, 7 = 29.4 Hz, 1H), 1.84 - 1.67 (m, 2H), 1.25 (s, 1H)
N-[4-(2,8- ¾ NMR (400 MHz, DMSO-D20) δ 7.70 - (ESI(+)) diazaspiro[4.5]dec-2- 7.49 (m, 2H), 7.45 - 7.32 (m, 3H), 7.22 - m/e 423 ylcarbonyl)phenyl] - 7.03 (m, 2H), 4.77 (d, 7 = 12.4 Hz, 4H), 3.53 (M+H)+
888
5-fluoro-l,3-dihydro- (t, 7 = 7.2 Hz, 2H), 3.33 (s, 2H), 2.79 (dd, 7
2H-isoindole-2- = 20.6, 14.7 Hz, 3H), 1.88 (s, 1H), 1.78 (t, 7 carboxamide = 7.1 Hz, 2H), 1.50 (s, 4H)
N-[4-(2,6- ¾ NMR (400 MHz, DMSO-D20) δ 7.70 - (ESI(+)) diazaspiro[4.5]dec-2- 7.54 (m, 2H), 7.50 - 7.30 (m, 3H), 7.24 - m/e 423 ylcarbonyl)phenyl] - 7.00 (m, 2H), 4.77 (d, 7 = 12.5 Hz, 4H), 3.75 (M+H)+
889 5-fluoro-l,3-dihydro- - 3.54 (m, 1H), 3.57 - 3.47 (m, 2H), 3.40 (d,
2H-isoindole-2- 7 = 11.8 Hz, 1H), 3.20 (d, 7 = 0.5 Hz, 1H), carboxamide 2.76 (d, 7 = 21.5 Hz, 2H), 2.07 - 1.77 (m,
3H), 1.64 - 1.40 (m, 6H)
N-[4-(2,7- ¾ NMR (400 MHz, DMSO-D20) δ 7.69 - (ESI(+)) diazaspiro [4.5] dec-7 - 7.54 (m, 2H), 7.37 (dd, 7 = 8.4, 5.2 Hz, 1H), m/e 423
890
ylcarbonyl)phenyl] - 7.33 - 7.22 (m, 2H), 7.23 - 7.02 (m, 2H), (M+H)+ 5-fluoro-l,3-dihydro- 4.77 (d, 7 = 12.2 Hz, 4H), 3.53 - 3.31 (m,
Figure imgf000690_0001
Figure imgf000691_0001
carboxamide 5-fluoro-N-[4-(2- ¾ NMR (400 MHz, DMSO-D20) δ 7.65 - (ESI(+)) oxa-7- 7.54 (m, 2H), 7.37 (dd, J = 8.3, 5.2 Hz, 1H), m/e 410 azaspiro [3.5]non-7- 7.35 - 7.23 (m, 2H), 7.22 - 7.03 (m, 2H), (M+H)+
905 ylcarbonyl)phenyl] - 4.77 (d, J = 12.4 Hz, 4H), 4.35 (s, 4H), 3.47
l,3-dihydro-2H- - 3.36 (m, 4H), 1.87 - 1.75 (m, 4H)
isoindole-2- carboxamide
5-fluoro-N-[4- ¾ NMR (400 MHz, DMSO-D20) δ 7.67 - (ESI(+))
(hexahydro-5H- 7.54 (m, 2H), 7.48 - 7.28 (m, 3H), 7.24 - m/e 396 furo[2,3-c]pyrrol-5- 6.92 (m, 2H), 4.77 (d, J = 12.4 Hz, 4H), 4.52 (M+H)+
906 ylcarbonyl)phenyl] - - 4.31 (m, 1H), 3.86 (dd, 7 = 15.5, 7.0 Hz,
l,3-dihydro-2H- 1H), 3.79 - 3.53 (m, 4H), 3.43 (dd, J = 11.7, isoindole-2- 5.3 Hz, 1H), 2.97 - 2.81 (m, 1H), 2.17 - 1.88 carboxamide (m, 1H), 1.88 - 1.59 (m, 1H)
5-fluoro-N-[4- ¾ NMR (400 MHz, DMSO-D20) δ 7.65 - (ESI(+)) (tetrahydro-lH- 7.54 (m, 2H), 7.54 - 7.31 (m, 3H), 7.26 - m/e 396 furo[3,4-c]pyrrol- 7.03 (m, 2H), 4.77 (d, J = 12.2 Hz, 4H), 3.74 (M+H)+ 5(3H)- (ddd, J = 19.7, 10.5, 7.2 Hz, 4H), 3.56 - 3.34
907
ylcarbonyl)phenyl] - (m, 4H), 3.01 - 2.84 (m, 2H)
l,3-dihydro-2H- isoindole-2- carboxamide
5-fluoro-N-[4- ¾ NMR (400 MHz, DMSO-D20) δ 7.59 (d, (ESI(+))
(hexahydrofuro [3,4- J = 8.7 Hz, 2H), 7.43 - 7.35 (m, 1H), 7.35 - m/e 410 c]pyridin-5(3H)- 7.24 (m, 2H), 7.22 - 7.05 (m, 2H), 4.77 (d, J (M+H)+
908 ylcarbonyl)phenyl] - = 12.5 Hz, 4H), 3.81 - 3.67 (m, 2H), 3.62 - l,3-dihydro-2H- 3.40 (m, 4H), 1.76 (s, 1H), 1.62 - 1.36 (m, isoindole-2- 1H), 1.28 - 1.08 (m, 2H)
carboxamide
N-(4- { [(lS)-l-(4- ¾ NMR (300 MHz, DMSO-d6) δ 8.59 (s, (ESI(+)) fluorophenyl)-2- 1H), 8.49 (d, J = 8.0 Hz, 1H), 7.87 - 7.79 m/e 420 hydroxy ethyl] c arb am (m, 2H), 7.72 - 7.65 (m, 2H), 7.47 - 7.28 (m, (M+H)+
976 oyl}phenyl)-l,3- 6H), 7.19 - 7.09 (m, 2H), 5.06 (d, J = 6.7
dihydro-2H- Hz, 1H), 4.95 - 4.87 (m, 1H), 4.79 (s, 4H), isoindole-2- 3.77 - 3.57 (m, 2H)
carboxamide
N-(4- { [(lS)-2- ¾ NMR (300 MHz, DMSO-d6) δ 8.58 (d, J (ESI(+)) hydroxy-l-(4- = 3.8 Hz, 1H), 8.42 (d, J = 8.1 Hz, 1H), 7.86 m/e 432 methoxyphenyl)ethyl - 7.76 (m, 3H), 7.69 (s, 1H), 7.69 - 7.61 (m, (M+H)+
977 ]carbamoyl jphenyl)- 2H), 7.41 - 7.27 (m, 6H), 6.91 - 6.84 (m,
l,3-dihydro-2H- 2H), 5.07 - 4.96 (m, 1H), 3.77 - 3.59 (m,
isoindole-2- 4H), 3.31 (s, 4H)
carboxamide
N-(4- { [(lS)-l-(l,3- ¾ NMR (300 MHz, DMSO-d6) δ 8.59 (s, (ESI(+)) benzodioxol-5-yl)-2- 1H), 8.39 (d, J = 8.1 Hz, 1H), 7.86 - 7.78 m/e 446 hydroxy ethyl] c arb am (m, 2H), 7.72 - 7.64 (m, 2H), 7.41 - 7.28 (m, (M+H)+ oyl}phenyl)-l,3- 4H), 6.99 (s, 1H), 6.87 - 6.82 (m, 2H), 5.97
978
dihydro-2H- (d, J = 2.3 Hz, 2H), 5.05 - 4.93 (m, 1H),
isoindole-2- 4.92 - 4.82 (m, 1H), 4.81 (d, J = 14.1 Hz,
carboxamide 4H), 3.73 - 3.53 (m, 2H)
5-fluoro-N-(4-{ [l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
1089 (l,3-thiazol-2- δ 7.78 - 7.64 (m, 2H), 7.64 - 7.53 (m, 2H), m/e 425 yl)propan-2- 7.52 - 7.34 (m, 1H), 7.28 - 7.16 (m, 1H), (M+H)+
Figure imgf000693_0001
carboxamide N-alpha-(4-{ [(5- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) fluoro- 1 ,3-dihydro- δ 7.76 - 7.64 (m, 2H), 7.64 - 7.52 (m, 2H), m/e 447 2H-isoindol-2- 7.44 - 7.31 (m, 1H), 7.31 - 7.21 (m, 4H), (M+H)+
1097
yl)carbonyl] amino }b 7.21 - 7.04 (m, 3H), 4.82 - 4.73 (m, 4H),
enzoyl)-D- 4.73 - 4.62 (m, 1H), 3.23 - 3.12 (m, 2H),
phenylalaninamide 3.07 - 2.93 (m, 2H)
N-(4-{ [2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
(acetylamino)phenyl] δ 7.96 - 7.78 (m, 2H), 7.77 - 7.64 (m, 3H), m/e 433 carbamoyl jphenyl)- 7.51 - 7.42 (m, 1H), 7.42 - 7.31 (m, 1H), (M+H)+
1098
5-fluoro-l,3-dihydro- 7.28 - 7.15 (m, 3H), 7.15 - 7.03 (m, 1H),
2H-isoindole-2- 4.86 - 4.70 (m, 4H), 2.09 (s, 3H)
carboxamide
5-fluoro-N-[4-({4-[2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) (2- δ 7.71 - 7.57 (m, 2H), 7.50 - 7.33 (m, 3H), m/e 457 hydroxyethoxy)ethyl 7.25 - 7.01 (m, 2H), 4.77 (d, J = 12.5 Hz, (M+H)+
]piperazin-l- 4H), 3.65 - 3.47 (m, 4H), 3.35 (dd, 7 = 12.2,
1099
yl } carbonyl)phenyl] - 7.3 Hz, 6H), 2.52 (dt, 7 = 3.8, 1.9 Hz, 2H)
l,3-dihydro-2H- isoindole-2- carboxamide
5-fluoro-N-(4-{ [2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
(furan-2-yl)-2- δ 7.76 - 7.67 (m, 3H), 7.66 - 7.53 (m, 2H), m/e 463
(pyrrolidin-1- 7.37 (dd, 7 = 8.4, 5.2 Hz, 1H), 7.25 - 7.02 (M+H)+
1100 yl)ethyl]carbamoyl}p (m, 2H), 6.78 (d, 7 = 3.3 Hz, 1H), 6.55 (dd, 7
henyl) - 1 , 3 - dihydro - = 3.3, 1.9 Hz, 1H), 4.89 - 4.68 (m, 6H), 4.08
2H-isoindole-2- - 3.94 (m, 1H), 3.87 (dd, 7 = 14.0, 7.4 Hz, carboxamide 1H), 3.43 (s, 1H), 2.00 - 1.78 (m, 4H)
N-{4-[bis(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methoxyethyl)carba δ 7.58 (d, J = 8.6 Hz, 2H), 7.37 (dd, 7 = 8.3, m/e 416 moyl]phenyl}-5- 5.1 Hz, 1H), 7.31 - 7.22 (m, 2H), 7.17 (d, 7 (M+H)+
1101
fluoro- 1 ,3-dihydro- = 8.9 Hz, 1H), 7.13 - 7.03 (m, 1H), 4.76 (d,
2H-isoindole-2- 7 = 12.5 Hz, 4H), 3.60 - 3.41 (m, 8H), 3.24 carboxamide (s, 6H)
N-{4-[(l-amino-l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) oxohexan-2- δ 7.87 - 7.71 (m, 2H), 7.64 (t, 7 = 10.2 Hz, m/e 413 yl)carbamoyl]phenyl 2H), 7.46 - 7.31 (m, 1H), 7.23 - 7.03 (m, (M+H)+
1102 }-5-fluoro-l,3- 2H), 4.78 (d, 7 = 12.5 Hz, 4H), 4.40 (dd, 7 =
dihydro-2H- 8.6, 5.6 Hz, 1H), 1.90 - 1.62 (m, 2H), 1.45 - isoindole-2- 1.18 (m, 4H), 0.87 (t, 7 = 6.9 Hz, 3H)
carboxamide
N-(4-{ [2-(3,4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) dimethoxypheny 1) eth δ 7.72 (d, 7 = 8.7 Hz, 2H), 7.60 (d, 7 = 8.7 m/e 464 yl]carbamoyl}phenyl Hz, 2H), 7.43 - 7.28 (m, 1H), 7.21 - 7.04 (M+H)+
1103 )-5-fluoro-l,3- (m, 2H), 6.91 - 6.81 (m, 2H), 6.81 - 6.69 (m,
dihydro-2H- 1H), 4.77 (d, 7 = 12.5 Hz, 4H), 3.73 (d, 7 =
isoindole-2- 2.5 Hz, 6H), 3.58 - 3.39 (m, 2H), 2.93 - 2.68 carboxamide (m, 2H)
N-(4-{ [(2S)-3,3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) dimethyl-1- δ 7.88 - 7.70 (m, 2H), 7.70 - 7.57 (m, 2H), m/e 427
(methylamino) - 1 - 7.45 - 7.30 (m, 1H), 7.26 - 7.01 (m, 2H), (M+H)+
1104 oxobutan-2- 4.78 (d, 7 = 12.6 Hz, 4H), 4.41 (d, 7 = 6.3
yl]carbamoyl}phenyl Hz, 1H), 2.64 (s, 3H), 1.03 (s, 9H)
)-5-fluoro-l,3- dihydro-2H- isoindole-2- carboxamide
N-alpha-(4-{ [(5- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) fluoro- 1 ,3-dihydro- δ 7.76 - 7.64 (m, 2H), 7.64 - 7.54 (m, 2H), m/e 447 2H-isoindol-2- 7.44 - 7.33 (m, 1H), 7.32 - 7.22 (m, 4H), (M+H)+
1105
yl)carbonyl] amino }b 7.25 - 7.13 (m, 3H), 7.12 - 6.99 (m, 1H),
enzoyl)-L- 4.81 - 4.71 (m, 4H), 4.71 - 4.61 (m, 1H),
phenylalaninamide 3.20 - 3.11 (m, 1H), 3.08 - 2.93 (m, 1H)
N-(4- { [(2R)-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) amino-4-methyl- 1 - δ 7.87 - 7.72 (m, 2H), 7.70 - 7.52 (m, 2H), m/e 413 oxopentan-2- 7.45 - 7.26 (m, 1H), 7.24 - 7.03 (m, 2H), (M+H)+ yl]carbamoyl}phenyl 4.78 (d, J = 12.6 Hz, 4H), 4.57 - 4.38 (m,
1106
)-5-fluoro-l,3- 1H), 1.90 - 1.47 (m, 3H), 1.07 - 0.71 (m,
dihydro-2H- 6H)
isoindole-2- carboxamide
-{4-[(4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) cyclohexylpiperazin- δ 7.76 - 7.57 (m, 2H), 7.51 - 7.32 (m, 3H), m/e 451 1- 7.23 - 7.03 (m, 2H), 4.77 (d, 7 = 12.4 Hz, (M+H)+
1107 yl)carbonyl]phenyl } - 4H), 3.88 (d, 7 = 76.9 Hz, 4H), 3.22 - 3.10
5-fluoro-l,3-dihydro- (m, 2H), 2.08 (d, 7 = 11.3 Hz, 2H), 1.86 (d, 7
2H-isoindole-2- = 13.1 Hz, 2H), 1.64 (d, 7 = 12.9 Hz, 1H),
carboxamide 1.54 - 1.17 (m, 6H), 1.17 - 1.04 (m, 1H)
5-fluoro-N-(4-{ [3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) (methylcarb amoyl)ph δ 8.16 (t, 7 = 1.8 Hz, 1H), 7.98 - 7.80 (m, m/e 433 enyl]carbamoyl }phe 3H), 7.74 - 7.59 (m, 2H), 7.59 - 7.47 (m, (M+H)+
1108
nyl)-l,3-dihydro-2H- 1H), 7.49 - 7.33 (m, 2H), 7.24 - 7.05 (m,
isoindole-2- 2H), 4.79 (d, 7 = 12.5 Hz, 4H), 2.83 (d, 7 =
carboxamide 3.6 Hz, 3H)
N-{4-[(2-amino-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) oxo-1- δ 7.90 - 7.72 (m, 2H), 7.64 (d, J = 8.7 Hz, m/e 433 phenylethyl)c arb amo 2H), 7.50 (d, 7 = 7.5 Hz, 2H), 7.43 - 7.26 (M+H)+
1109 yl]phenyl } -5-fluoro- (m, 4H), 7.20 - 7.02 (m, 2H), 5.62 (s, 1H),
l,3-dihydro-2H- 4.77 (d, 7 = 12.5 Hz, 4H)
isoindole-2- carboxamide
N-{4-[(3-tert- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) butoxypropyl)carbam δ 7.79 - 7.66 (m, 2H), 7.66 - 7.53 (m, 2H), m/e 414 oyl]phenyl} -5- 7.37 (dd, 7 = 8.4, 5.1 Hz, 1H), 7.27 - 7.02 (M+H)+
1110
fluoro- 1 ,3-dihydro- (m, 2H), 4.77 (d, 7 = 12.4 Hz, 4H), 3.44 -
2H-isoindole-2- 3.35 (m, 2H), 3.31 (dd, 7 = 16.4, 9.5 Hz,
carboxamide 2H), 1.73 (p, 7 = 6.6 Hz, 2H), 1.15 (s, 9H)
N-(4- { [2-(2,6- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) dimethylmorpholin- δ 7.86 - 7.72 (m, 2H), 7.69 - 7.55 (m, 2H), m/e 441
4- 7.47 - 7.32 (m, 1H), 7.24 - 6.96 (m, 2H), (M+H)+ yl)ethyl]carbamoyl}p 4.78 (d, 7 = 12.5 Hz, 4H), 3.92 - 3.76 (m,
1111
henyl)-5-fluoro-l,3- 2H), 3.67 (t, 7 = 6.2 Hz, 2H), 3.52 (d, 7 =
dihydro-2H- 12.0 Hz, 2H), 3.31 (dd, 7 = 13.3, 7.0 Hz,
isoindole-2- 3H), 2.71 (t, 7 = 11.7 Hz, 2H), 1.17 (d, 7 =
carboxamide 6.3 Hz, 6H)
N-(4- { [(lR)-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
1112 amino-2-oxo-l- δ 7.87 - 7.70 (m, 2H), 7.70 - 7.56 (m, 2H), m/e 433 phenylethyl] c arb amo 7.51 (dd, 7 = 11.1, 9.7 Hz, 2H), 7.44 - 7.25 (M+H)+
Figure imgf000696_0001
carboxamide 46.1 Hz, 6H), 1.46 (s, 2H)
Figure imgf000697_0001
carboxamide Ν-(4-{ [1- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
(ethylamino)-l- δ 7.87 - 7.71 (m, 2H), 7.71 - 7.53 (m, 2H), m/e 399 oxopropan-2- 7.49 - 7.24 (m, 1H), 7.25 - 6.98 (m, 2H), (M+H)+ yl]carbamoyl}phenyl 4.77 (d, 7 = 12.4 Hz, 4H), 4.55 - 4.28 (m,
1152
)-5-fluoro-l,3- 1H), 3.19 - 3.02 (m, 2H), 3.01 - 2.74 (m,
dihydro-2H- 3H), 1.96 (s, 1H), 1.34 (d, 7 = 7.1 Hz, 3H), isoindole-2- 1.04 (t, 7 = 7.2 Hz, 2H)
carboxamide
5-fluoro-N-(4-{ [(l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methyl- 1 H-pyrazol- δ 7.89 - 7.69 (m, 2H), 7.69 - 7.57 (m, 3H), m/e 394 3- 7.50 (d, 7 = 2.1 Hz, 1H), 7.42 - 7.22 (m, (M+H)+ yl)methyl]carbamoyl 2H), 7.25 - 7.00 (m, 2H), 4.77 (d, 7 = 12.4
1153
}phenyl)-l,3- Hz, 4H), 4.41 (s, 2H), 3.78 (s, 3H), 2.97 (s, dihydro-2H- 2H)
isoindole-2- carboxamide
5-fluoro-N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methoxybutyl)carba δ 7.78 - 7.72 (m, 2H), 7.64 - 7.58 (m, 2H), m/e 386 moyl] phenyl } - 1 , 3 - 7.37 (dd, 7 = 8.4, 5.1 Hz, 1H), 7.17 (dd, 7 = (M+H)+
1154 dihydro-2H- 9.1, 2.4 Hz, 1H), 7.10 (td, 7 = 8.9, 2.5 Hz,
isoindole-2- 1H), 4.79 (bs, 3H), 4.76 (bs, 3H), 3.38 - 3.32 carboxamide (m, 5H), 3.32 (s, 4H), 1.61 - 1.39 (m, 2H),
0.90 (t, 7 = 7.4 Hz, 3H)
N-(4-{ [4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
(dimethylamino)buty δ 7.86 - 7.69 (m, 2H), 7.70 - 7.54 (m, 2H), m/e 399
1] carbamoyl } phenyl) 7.44 - 7.27 (m, 1H), 7.23 - 7.00 (m, 2H), (M+H)+
1155 -5-fluoro-l,3- 4.77 (d, 7 = 12.5 Hz, 4H), 3.31 (dd, 7 = 13.0,
dihydro-2H- 6.3 Hz, 2H), 3.19 - 2.99 (m, 3H), 2.79 (s,
isoindole-2- 7H), 1.71 - 1.50 (m, 4H)
carboxamide
5-fluoro-N-{4-[(3S)- ¾ NMR (400 MHz DMSO- , Temp=90°C) (ESI(+)) tetrahydrofuran-3 - δ 7.82 - 7.70 (m, 2H), 7.70 - 7.54 (m, 2H), m/e 370 ylcarbamoyl]phenyl } 7.44 - 7.28 (m, 1H), 7.23 - 7.03 (m, 2H), (M+H)+ -l,3-dihydro-2H- 4.77 (d, 7 = 12.5 Hz, 4H), 4.53 - 4.35 (m,
1156
isoindole-2- 1H), 3.98 - 3.81 (m, 2H), 3.77 - 3.66 (m,
carboxamide 1H), 3.70 - 3.53 (m, 1H), 3.01 - 2.87 (m,
1H), 2.32 - 2.10 (m, 1H), 2.07 - 1.81 (m,
1H)
5-fluoro-N-{4-[(l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methoxybutan-2- δ 7.78 - 7.72 (m, 2H), 7.63 - 7.57 (m, 2H), m/e 386 yl)carbamoyl]phenyl 7.40 - 7.31 (m, 1H), 7.21 - 7.04 (m, 2H), (M+H)+
1157
}-l,3-dihydro-2H- 4.77 (d, 7 = 12.4 Hz, 4H), 4.11 - 3.94 (m,
isoindole-2- 1H), 3.55 - 3.32 (m, 2H), 3.28 (s, 3H), 1.72 carboxamide - 1.39 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H)
N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) ethoxypropyl)carbam δ 7.83 - 7.70 (m, 2H), 7.69 - 7.51 (m, 2H), m/e 386 oyl]phenyl}-5- 7.48 - 7.29 (m, 1H), 7.25 - 7.00 (m, 2H), (M+H)+
1158
fluoro- 1 ,3-dihydro- 4.77 (d, 7 = 12.5 Hz, 4H), 3.71 - 3.55 (m,
2H-isoindole-2- 1H), 3.58 - 3.40 (m, 2H), 3.40 - 3.29 (m,
carboxamide 1H), 1.26 - 0.98 (m, 6H)
N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
[benzyl(methyl)carba δ 7.69 - 7.53 (m, 2H), 7.42 - 7.29 (m, 6H), m/e 404
1159
moyl]phenyl}-5- 7.28 (dd, 7 = 13.0, 7.2 Hz, 3H), 7.19 - 7.01 (M+H)+ fluoro- 1 ,3-dihydro- (m, 2H), 4.76 (d, 7 = 12.4 Hz, 4H), 4.58 (d, 7 2H-isoindole-2- = 21.5 Hz, 3H), 2.89 (d, J = 3.2 Hz, 3H)
carboxamide
N-{4-[(2S)-butan-2- ¾ NMR (400 MHz, DMSO_D20) δ 7.83 - (ESI(+)) ylcarbamoyl]phenyl } 7.68 (m, 2H), 7.66 - 7.54 (m, 2H), 7.37 (dd, m/e 356
-5-fluoro-l,3- 7 = 8.4, 5.2 Hz, IH), 7.20 - 7.12 (m, IH), (M+H)+
1160 dihydro-2H- 7.12 - 7.01 (m, IH), 4.77 (d, 7 = 12.5 Hz,
isoindole-2- 4H), 3.92 (h, 7 = 6.6 Hz, IH), 1.70 - 1.41
carboxamide (m, 2H), 1.15 (d, 7 = 6.6 Hz, 3H), 0.88 (t, 7 =
7.4 Hz, 3H)
5-fluoro-N-(4-{ [2-(5- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methyl- 1 H-pyrazol- δ 7.83 - 7.68 (m, 2H), 7.66 - 7.54 (m, 2H), m/e 408 1- 7.37 (dd, 7 = 8.4, 5.2 Hz, IH), 7.20 - 7.12 (M+H)+
1161 yl)ethyl]carbamoyl}p (m, IH), 7.12 - 7.01 (m, IH), 4.77 (d, 7 =
henyl) - 1 , 3 - dihydro - 12.5 Hz, 4H), 3.92 (h, 7 = 6.6 Hz, 4H), 0.88
2H-isoindole-2- (t, 7 = 7.4 Hz, 3H)
carboxamide
5-fluoro-N-(4-{ [2-(3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methyl- 1 H-pyrazol- δ 7.77 - 7.66 (m, 2H), 7.66 - 7.56 (m, 2H), m/e 408 1- 7.50 (d, 7 = 2.1 Hz, IH), 7.44 - 7.29 (m, (M+H)+ yl)ethyl]carbamoyl}p IH), 7.17 (dd, 7 = 9.0, 2.2 Hz, IH), 7.14 -
1162
henyl) - 1 , 3 - dihydro - 7.00 (m, IH), 6.00 (d, 7 = 2.2 Hz, IH), 4.77
2H-isoindole-2- (d, 7 = 12.5 Hz, 4H), 4.21 (t, 7 = 6.4 Hz, 2H), carboxamide 3.63 (t, 7 = 6.4 Hz, 2H), 2.89 (d, 7 = 62.0 Hz,
IH), 2.21 (d, 7 = 32.8 Hz, 3H)
5-fluoro-N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methylpropyl)carbam δ 7.82 - 7.69 (m, 2H), 7.69 - 7.54 (m, 2H), m/e 356 oyl]phenyl}-l,3- 7.46 - 7.26 (m, IH), 7.29 - 7.01 (m, 2H), (M+H)+
1163 dihydro-2H- 4.77 (d, 7 = 12.4 Hz, 4H), 3.15 - 3.05 (m,
isoindole-2- 2H), 2.98 - 2.75 (m, 3H), 2.06 - 1.89 (m,
carboxamide 2H), 1.92 - 1.78 (m, IH), 0.90 (d, 7 = 6.7
Hz, 7H)
5-fluoro-N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
[(pyridin-3- δ 8.79 - 8.58 (m, 2H), 8.19 (t, 7 = 7.0 Hz, m/e 391 ylmethyl)carbamoyl] IH), 7.84 - 7.73 (m, 2H), 7.73 - 7.66 (m, (M+H)+
1164
phenyl } - 1 , 3 -dihydro - IH), 7.70 - 7.55 (m, 2H), 7.50 - 7.27 (m,
2H-isoindole-2- IH), 7.27 - 7.06 (m, 2H), 4.77 (d, 7 = 12.4
carboxamide Hz, 4H), 4.59 (s, 2H)
5-fluoro-N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
[(tetrahydrofuran-2- δ 7.85 - 7.72 (m, 2H), 7.66 - 7.53 (m, 2H), m/e 384 ylmethyl)carbamoyl] 7.46 - 7.32 (m, IH), 7.24 - 7.14 (m, IH), (M+H)+
1165 phenyl } - 1 , 3 -dihydro - 7.14 - 7.04 (m, IH), 4.93 - 4.61 (m, 4H),
2H-isoindole-2- 4.11 - 3.90 (m, IH), 3.87 - 3.72 (m, IH),
carboxamide 3.72 - 3.53 (m, IH), 3.35 (t, 7 = 7.5 Hz, 2H),
2.06 - 1.73 (m, 3H), 1.66 - 1.52 (m, IH)
N-(4-{ [(lR)-l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) cyclopropylethyl]car δ 7.83 - 7.72 (m, 2H), 7.68 - 7.57 (m, 2H), m/e 368 bamoyl } phenyl) -5 - 7.37 (dd, 7 = 8.3, 5.1 Hz, IH), 7.23 - 7.02 (M+H)+
1166 fluoro- 1 ,3-dihydro- (m, 2H), 4.77 (d, 7 = 12.5 Hz, 4H), 3.63 - 2H-isoindole-2- 3.42 (m, IH), 1.22 (d, 7 = 6.7 Hz, 3H), 1.15 carboxamide - 0.79 (m, IH), 0.51 - 0.24 (m, 3H), 0.24 - 0.11 (m, IH)
5-fluoro-N-(4-{ [l-(l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
1167 methylcyclopropyl)et δ 7.83 - 7.68 (m, 2H), 7.68 - 7.54 (m, 2H), m/e 382
Figure imgf000700_0001
Figure imgf000701_0001
5-fluoro-N-{4-[(2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methoxyethyl)carba δ 7.78 - 7.72 (m, 1H), 7.64 - 7.56 (m, 1H), m/e 358 moyl] phenyl } - 1 , 3 - 7.41 - 7.28 (m, 1H), 7.20 - 7.05 (m, 1H), (M+H)+
1182
dihydro-2H- 4.78 (bs, 1H), 4.75 (bs, 1H), 3.49 (d, 7 = 5.2 isoindole-2- Hz, 1H), 3.48 - 3.39 (m, 1H), 2.97 (s, 2H), carboxamide 2.88 - 2.76 (m, 1H), 1.96 (s, 1H)
N-[4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
(cyclopentylcarbamo δ 7.83 - 7.68 (m, 2H), 7.68 - 7.53 (m, 2H), m/e 368 yl)phenyl] -5 -fluoro- 7.51 - 7.28 (m, 1H), 7.20 - 7.13 (m, 1H), (M+H)+
1183 l,3-dihydro-2H- 7.12 - 7.03 (m, 1H), 4.77 (d, 7 = 12.4 Hz,
isoindole-2- 4H), 4.33 - 4.12 (m, 1H), 2.00 - 1.84 (m,
carboxamide 2H), 1.82 - 1.66 (m, 2H), 1.66 - 1.45 (m,
4H)
5-fluoro-N-(4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
{ [(2S)-3- δ 7.85 - 7.69 (m, 2H), 7.66 - 7.53 (m, 2H), m/e 370 methylbutan-2- 7.46 - 7.31 (m, 1H), 7.23 - 7.16 (m, 1H), (M+H)+
1184 yl]carbamoyl}phenyl 7.16 - 7.05 (m, 1H), 4.77 (d, 7 = 12.5 Hz,
)-l,3-dihydro-2H- 4H), 3.85 - 3.79 (m, 1H), 1.89 - 1.72 (m,
isoindole-2- 1H), 1.11 (t, 7 = 5.6 Hz, 3H), 0.90 (dd, 7 =
carboxamide 6.8, 1.1 Hz, 6H)
5-fluoro-N-(4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
{ [(2R)-3- δ 7.87 - 7.68 (m, 2H), 7.68 - 7.50 (m, 2H), m/e 370 methylbutan-2- 7.37 (dd, 7 = 8.4, 5.2 Hz, 1H), 7.24 - 7.15 (M+H)+
1185 yl]carbamoyl}phenyl (m, 1H), 7.15 - 7.05 (m, 1H), 4.77 (d, 7 =
)-l,3-dihydro-2H- 12.5 Hz, 4H), 3.83 (p, 7 = 6.7 Hz, 1H), 1.88 isoindole-2- - 1.63 (m, 1H), 1.12 (d, 7 = 6.8 Hz, 3H),
carboxamide 0.90 (dd, 7 = 6.8, 1.4 Hz, 6H)
5-fluoro-N-(4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) { [(2S)-2- δ 7.84 - 7.70 (m, 2H), 7.70 - 7.56 (m, 2H), m/e 370 methylbutyl]carbamo 7.46 - 7.27 (m, 1H), 7.25 - 7.03 (m, 2H), (M+H)+
1186 yl } phenyl) -1,3 - 4.77 (d, 7 = 12.5 Hz, 4H), 3.21 (dd, 7 = 13.1,
dihydro-2H- 6.4 Hz, 1H), 3.15 - 2.97 (m, 1H), 1.80 - 1.61 isoindole-2- (m, 1H), 1.53 - 1.30 (m, 1H), 1.28 - 1.06 (m, carboxamide 1H), 0.98 - 0.79 (m, 6H)
5-fluoro-N-{4-[(2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) hydroxy-2- δ 7.81 - 7.71 (m, 2H), 7.67 - 7.57 (m, 2H), m/e 372 methylpropyl)carbam 7.45 - 7.27 (m, 1H), 7.21 - 7.13 (m, 1H), (M+H)+
1187 oyl]phenyl}-l,3- 7.13 - 7.00 (m, 1H), 4.83 - 4.70 (m, 4H),
dihydro-2H- 1.96 (s, 2H), 1.14 (s, 6H)
isoindole-2- carboxamide
5-fluoro-N-(4-{ [2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
(tetrahydro-2H- δ 7.82 - 7.67 (m, 2H), 7.69 - 7.51 (m, 2H), m/e 412 pyran-4- 7.43 - 7.32 (m, 1H), 7.21 - 7.01 (m, 2H), (M+H)+
1188 yl)ethyl]carbamoyl}p 4.78 (t, 7 = 10.2 Hz, 4H), 3.95 - 3.70 (m,
henyl) - 1 , 3 - dihydro - 2H), 3.38 - 3.30 (m, 2H), 1.96 (s, 1H), 1.65
2H-isoindole-2- - 1.55 (m, 2H), 1.57 - 1.43 (m, 2H), 1.29 - carboxamide 1.09 (m, 2H)
N-[4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
(butylcarbamoyl)phe δ 7.81 - 7.69 (m, 2H), 7.68 - 7.53 (m, 2H), m/e 356 nyl]-5-fluoro-l,3- 7.47 - 7.30 (m, 1H), 7.26 - 7.13 (m, 1H), (M+H)+
1189
dihydro-2H- 7.13 - 7.01 (m, 1H), 4.87 - 4.67 (m, 4H),
isoindole-2- 3.27 (d, 7 = 7.1 Hz, 2H), 1.61 - 1.45 (m,
carboxamide 2H), 1.44 - 1.26 (m, 2H), 0.91 (t, 7 = 7.3 Hz, 3H)
5-fluoro-N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
[methyl(tetrahydrofu δ 7.69 - 7.52 (m, 2H), 7.42 - 7.31 (m, IH), m/e 398 ran-2- 7.32 - 7.24 (m, 2H), 7.20 - 7.14 (m, IH), (M+H)+
1190 ylmethyl)carbamoyl] 7.14 - 7.02 (m, IH), 4.89 - 4.63 (m, 4H),
phenyl } - 1 , 3 -dihydro - 4.12 - 3.96 (m, IH), 3.82 - 3.58 (m, 2H),
2H-isoindole-2- 3.59 - 3.34 (m, 2H), 2.00 - 1.86 (m, 2H),
carboxamide 1.86 - 1.72 (m, 2H), 1.61 - 1.33 (m, IH)
5-fluoro-N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methoxyethyl)(methy δ 7.69 - 7.53 (m, 2H), 7.43 - 7.32 (m, IH), m/e 372 l)carbamoyl]phenyl } 7.32 - 7.24 (m, 2H), 7.19 - 7.13 (m, IH), (M+H)+
1191
-l,3-dihydro-2H- 7.13 - 7.03 (m, IH), 4.77 (d, J = 12.4 Hz,
isoindole-2- 4H), 3.52 (s, 3H), 3.03 - 2.92 (m, 3H)
carboxamide
N-{4-[(l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) cyanoethyl)carbamoy δ 7.89 - 7.74 (m, 2H), 7.74 - 7.57 (m, 2H), m/e 353 1] phenyl } -5 -fluoro - 7.37 (dd, J = 8.4, 5.1 Hz, IH), 7.17 (dd, J = (M+H)+
1192
l,3-dihydro-2H- 9.0, 2.2 Hz, IH), 7.13 - 7.04 (m, IH), 4.93
isoindole-2- (q, J = 7.2 Hz, IH), 4.78 (d, J = 12.4 Hz,
carboxamide 4H), 1.57 (d, 7 = 7.2 Hz, 3H)
5-fluoro-N-(4-{ [(5- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methyl- 1 ,2-oxazol-3 - δ 7.85 - 7.72 (m, 2H), 7.68 - 7.56 (m, 2H), m/e 395 yl)methyl]carbamoyl 7.42 - 7.28 (m, IH), 7.21 - 7.12 (m, IH), (M+H)+
1193 }phenyl)-l,3- 7.12 - 7.01 (m, IH), 6.24 - 6.00 (m, IH),
dihydro-2H- 4.90 - 4.68 (m, 4H), 4.55 - 4.37 (m, 2H),
isoindole-2- 2.42 - 2.27 (m, 3H)
carboxamide
5-fluoro-N-{4-[(3R)- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) tetrahydrofuran-3 - δ 7.87 - 7.72 (m, 2H), 7.66 - 7.55 (m, 2H), m/e 370 ylcarbamoyl]phenyl } 7.45 - 7.32 (m, IH), 7.17 (dd, J = 9.0, 2.1 (M+H)+ -l,3-dihydro-2H- Hz, IH), 7.14 - 7.01 (m, IH), 4.77 (d, J =
1194
isoindole-2- 12.4 Hz, 4H), 4.50 - 4.38 (m, IH), 3.93 - carboxamide 3.80 (m, 2H), 3.80 - 3.66 (m, IH), 3.59 (dd,
J = 8.9, 4.6 Hz, IH), 2.27 - 2.09 (m, IH),
1.99 - 1.77 (m, IH)
N-{4-[(3-methoxy- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) 2,2- δ 7.80 - 7.70 (m, 2H), 7.68 - 7.52 (m, 2H), m/e 382 dimethylpropyl)carba 7.44 - 7.23 (m, 4H), 4.79 (s, 4H), 3.29 (d, J (M+H)+
1260 moyl] phenyl } - 1 , 3 - = 7.7 Hz, 3H), 3.22 - 3.19 (m, 2H), 3.15 (s,
dihydro-2H- 2H), 0.90 (s, 6H)
isoindole-2- carboxamide
N-{4-[(4,4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) difluorocyclohexyl)c δ 7.86 - 7.69 (m, 2H), 7.69 - 7.50 (m, 2H), m/e 382 arbamoyl]phenyl } - 7.38 - 7.22 (m, 4H), 4.99 - 4.62 (m, 4H), (M+H)+
1261
l,3-dihydro-2H- 3.96 (s, IH), 2.20 - 1.82 (m, 6H), 1.70 (t, J =
isoindole-2- 11.7 Hz, 2H)
carboxamide
N-(4-{ [(2R)-l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) cyanobutan-2- δ 7.87 - 7.70 (m, 2H), 7.73 - 7.49 (m, 2H), m/e 362
1262
yl]carbamoyl}phenyl 7.45 - 7.17 (m, 4H), 4.80 (s, 4H), 4.23 - 3.99 (M+H)+ )-l,3-dihydro-2H- (m, IH), 2.97 - 2.63 (m, 2H), 1.78 - 1.56 (m, isoindole-2- 2H), 0.91 (q, 7 = 7.2 Hz, 3H) carboxamide
N-{4-[(2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methoxybutyl)carba δ 7.77 - 7.70 (m, 2H), 7.69 - 7.52 (m, 2H), m/e 368 moyl] phenyl } - 1 , 3 - 7.42 - 7.22 (m, 4H), 4.79 (s, 4H), 3.41 - 3.31 (M+H)+
1263
dihydro-2H- (m, 5H), 1.65 - 1.30 (m, 2H), 0.90 (t, 7 = 7.4 isoindole-2- Hz, 3H)
carboxamide
N-(4-{ [l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
(ethylamino)-l- δ 7.88 - 7.73 (m, 2H), 7.69 - 7.55 (m, 2H), m/e 381 oxopropan-2- 7.48 - 7.16 (m, 4H), 4.80 (s, 4H), 4.58 - 4.35 (M+H)+
1264 yl]carbamoyl}phenyl (m, 1H), 3.13 (q, 7 = 7.2 Hz, 2H), 1.35 (d, 7
)-l,3-dihydro-2H- = 7.2 Hz, 3H), 1.05 (t, 7 = 7.2 Hz, 3H)
isoindole-2- carboxamide
N-(4-{ [2-methyl-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) (morpholin-4- δ 7.95 - 7.77 (m, 2H), 7.70 (t, 7 = 10.6 Hz, m/e 437 yl)butyl] carbamoyl } 2H), 7.48 - 7.20 (m, 4H), 4.80 (s, 4H), 3.95 (M+H)+
1265
phenyl)- 1 ,3-dihydro- (d, 7 = 20.8 Hz, 4H), 3.75 - 3.55 (m, 2H),
2H-isoindole-2- 3.40 (s, 2H), 1.95 - 1.63 (m, 2H), 1.34 (s,
carboxamide 3H), 1.02 (t, 7 = 7.4 Hz, 3H)
N-(4-{ [(lR)-l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) cyclopropylethyl]car δ 7.86 - 7.69 (m, 2H), 7.69 - 7.53 (m, 2H), m/e 350 b amoyl } phenyl) - 1 , 3 - 7.49 - 7.13 (m, 4H), 4.79 (s, 4H), 3.63 - 3.44 (M+H)+
1266
dihydro-2H- (m, 1H), 1.22 (d, 7 = 6.7 Hz, 3H), 1.09 - isoindole-2- 0.90 (m, 1H), 0.57 - 0.12 (m, 4H)
carboxamide
N-(4-{ [(lS)-l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) cyclopropylethyl]car δ 7.84 - 7.71 (m, 2H), 7.66 - 7.55 (m, 2H), m/e 350 b amoyl } phenyl) - 1 , 3 - 7.40 - 7.19 (m, 4H), 4.79 (s, 4H), 3.52 (p, 7 (M+H)+
1267
dihydro-2H- = 6.9 Hz, 1H), 1.22 (d, 7 = 6.7 Hz, 3H), 1.13 isoindole-2- - 0.90 (m, 1H), 0.54 - 0.14 (m, 4H)
carboxamide
N-{4-[(3S)- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) tetrahydrofuran-3 - δ 7.84 - 7.73 (m, 2H), 7.67 - 7.53 (m, 2H), m/e 351 ylcarbamoyl]phenyl } 7.42 - 7.19 (m, 4H), 4.80 (d, 7 = 5.5 Hz, (M+H)+
1269 -l,3-dihydro-2H- 4H), 4.52 - 4.35 (m, 1H), 3.93 - 3.78 (m,
isoindole-2- 2H), 3.78 - 3.67 (m, 1H), 3.63 - 3.52 (m,
carboxamide 1H), 2.29 - 2.08 (m, 1H), 2.07 - 1.79 (m,
1H)
N-(4-{ [2-(tetrahydro- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
2H-pyran-3- δ 7.82 - 7.69 (m, 2H), 7.65 - 7.48 (m, 2H), m/e 394 yl)ethyl]carbamoyl}p 7.50 - 7.14 (m, 4H), 4.79 (s, 4H), 3.93 - 3.60 (M+H)+
1270
henyl) - 1 , 3 - dihydro - (m, 2H), 3.41 - 3.29 (m, 2H), 3.14 - 2.93 (m,
2H-isoindole-2- 1H), 2.02 - 1.79 (m, 1H), 1.69 - 1.43 (m,
carboxamide 4H), 1.29 - 1.09 (m, 1H)
N-(4-{ [(5-methyl- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) l,3-oxazol-2- δ 7.92 - 7.71 (m, 2H), 7.72 - 7.56 (m, 2H), m/e 377 yl)methyl]carbamoyl 7.46 - 7.24 (m, 4H), 4.80 (d, 7 = 1.4 Hz, (M+H)+
1271 }phenyl)-l,3- 4H), 4.63 - 4.41 (m, 2H), 2.26 (t, 7 = 2.3 Hz,
dihydro-2H- 3H)
isoindole-2- carboxamide N-[4-({2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
[(dimethylamino)met δ 7.85 - 7.75 (m, 2H), 7.72 - 7.63 (m, 2H), m/e 429 hyl]benzyl } carbamo 7.59 - 7.50 (m, 1H), 7.50 - 7.42 (m, 2H), (M+H)+
1272 yl)phenyl]-l,3- 7.42 - 7.24 (m, 5H), 4.79 (s, 4H), 4.52 (d, J
dihydro-2H- = 16.7 Hz, 4H), 2.88 (s, 6H)
isoindole-2- carboxamide
N-(4-{ [(lR)-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) amino-2-oxo-l- δ 7.86 - 7.76 (m, 2H), 7.70 - 7.62 (m, 2H), m/e 415 phenylethyl] c arb amo 7.51 (t, J = 6.8 Hz, 2H), 7.40 - 7.25 (m, 7H), (M+H)+
1273 yl } phenyl) -1,3 - 5.63 (s, 1H), 4.79 (s, 4H)
dihydro-2H- isoindole-2- carboxamide
N-[4-(l,3-oxazol-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) ylcarbamoyl)phenyl] δ 8.03 - 7.85 (m, 2H), 7.85 - 7.76 (m, 1H), m/e 329
1274 -l,3-dihydro-2H- 7.76 - 7.61 (m, 2H), 7.47 - 7.25 (m, 4H), (M+H)+ isoindole-2- 7.18 - 7.03 (m, 1H), 4.92 - 4.62 (m, 4H)
carboxamide
N-[4-(tetrahydro-2H- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) pyran-3- δ 7.88 - 7.65 (m, 2H), 7.69 - 7.53 (m, 2H), m/e 366 ylcarbamoyl)phenyl] 7.46 - 7.18 (m, 4H), 4.79 (s, 4H), 3.99 - 3.66 (M+H)+
1275
-l,3-dihydro-2H- (m, 3H), 3.44 - 3.32 (m, 1H), 2.04 - 1.86 (m, isoindole-2- 1H), 1.84 - 1.50 (m, 3H)
carboxamide
N-(4-{ [2-(2,6- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) dimethylmorpholin- δ 7.85 - 7.70 (m, 2H), 7.70 - 7.57 (m, 2H), m/e 423
4- 7.45 - 7.22 (m, 4H), 4.80 (s, 4H), 3.94 - 3.77 (M+H)+
1276 yl)ethyl]carbamoyl}p (m, 2H), 3.67 (t, J = 6.2 Hz, 2H), 3.53 (d, J =
henyl) - 1 , 3 - dihydro - 12.0 Hz, 2H), 3.32 (dd, J = 12.8, 6.6 Hz,
2H-isoindole-2- 3H), 2.72 (t, J = 11.7 Hz, 2H), 1.18 (d, J =
carboxamide 6.3 Hz, 6H)
N-(4-{ [l-(l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) methylcyclopropyl)et δ 7.85 - 7.69 (m, 2H), 7.69 - 7.53 (m, 2H), m/e 364 hyl]carbamoyl }phen 7.47 - 6.99 (m, 4H), 4.79 (s, 4H), 3.82 - 3.62 (M+H)+
1277
yl)-l,3-dihydro-2H- (m, 1H), 1.17 (d, 7 = 6.9 Hz, 3H), 1.07 (s,
isoindole-2- 3H), 0.69 - 0.53 (m, 1H), 0.47 - 0.35 (m,
carboxamide 1H), 0.29 - 0.13 (m, 2H)
N-(4-{ [2-(furan-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) yl)-2-(pyrrolidin- 1 - δ 7.79 - 7.65 (m, 3H), 7.68 - 7.54 (m, 2H), m/e 445 yl)ethyl]carbamoyl}p 7.43 - 7.17 (m, 4H), 6.78 (d, J = 3.3 Hz, (M+H)+
1278
henyl) - 1 , 3 - dihydro - 1H), 6.64 - 6.46 (m, 1H), 4.91 - 4.72 (m,
2H-isoindole-2- 5H), 4.11 - 3.93 (m, 1H), 3.93 - 3.77 (m,
carboxamide 1H), 2.01 - 1.76 (m, 4H)
N-(4-{ [3-(3,5- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) dimethyl-lH- δ 7.80 - 7.69 (m, 2H), 7.69 - 7.51 (m, 2H), m/e 418 pyrazol-1- 7.44 - 7.25 (m, 4H), 4.79 (s, 4H), 4.03 - 3.87 (M+H)+ yl)propyl] carbamoyl (m, 2H), 2.23 - 2.15 (m, 3H), 2.10 (s, 3H),
1310
}phenyl)-l,3- 2.05 - 1.88 (m, 2H)
dihydro-2H- isoindole-2- carboxamide N-(4-{ [(3S)-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methyl-2-oxoazepan- δ 7.92 - 7.83 (m, 1H), 7.79 - 7.70 (m, 2H), m/e 407
3- 7.70 - 7.57 (m, 2H), 7.46 - 7.13 (m, 5H), (M+H)+
1311 yl]carbamoyl}phenyl 6.63 - 6.61 (m, 1H), 4.90 - 4.73 (m, 6H),
)-l,3-dihydro-2H- 3.76 - 3.57 (m, 1H), 2.95 (s, 3H), 2.02 - 1.68 isoindole-2- (m, 4H), 1.64 - 1.32 (m, 2H)
carboxamide
N-(4-{ [2-(lH- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) pyrazol-1- δ 7.74 - 7.67 (m, 2H), 7.66 - 7.59 (m, 3H), m/e 376 yl)ethyl]carbamoyl}p 7.39 - 7.28 (m, 4H), 6.23 (t, J = 2.0 Hz, 1H), (M+H)+
1312
henyl) - 1 , 3 - dihydro - 4.79 (s, 4H), 4.31 (t, 7 = 6.4 Hz, 2H), 3.66 (t,
2H-isoindole-2- 7 = 6.4 Hz, 2H)
carboxamide
N-(4-{ [l-(l,3- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) thiazol-2- δ 7.91 - 7.75 (m, 2H), 7.74 - 7.62 (m, 3H), m/e 393 yl)ethyl]carbamoyl}p 7.53 (d, 7 = 3.3 Hz, 1H), 7.47 - 7.23 (m, (M+H)+
1313
henyl) - 1 , 3 - dihydro - 4H), 5.56 - 5.34 (m, 1H), 4.80 (s, 4H), 1.65
2H-isoindole-2- (d, 7 = 7.0 Hz, 3H)
carboxamide
N-(4-{ [l-(furan-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) yl)propan-2- δ 7.77 - 7.66 (m, 2H), 7.66 - 7.55 (m, 2H), m/e 390 yl]carbamoyl}phenyl 7.50 - 7.39 (m, 1H), 7.41 - 7.19 (m, 4H), (M+H)+
1314 )-l,3-dihydro-2H- 6.45 - 6.23 (m, 1H), 6.13 (d, 7 = 3.1 Hz,
isoindole-2- 1H), 4.79 (s, 4H), 4.39 - 4.14 (m, 1H), 3.03 carboxamide - 2.87 (m, 1H), 2.87 - 2.70 (m, 1H), 1.19 (d,
7 = 6.7 Hz, 3H)
N-(4-{ [l-(l-methyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) lH-pyrazol-4- δ 7.81 - 7.68 (m, 2H), 7.70 - 7.57 (m, 2H), m/e 390 yl)ethyl]carbamoyl}p 7.54 (s, 1H), 7.47 - 7.20 (m, 4H), 5.14 (q, 7 (M+H)+
1315
henyl) - 1 , 3 - dihydro - = 6.9 Hz, 1H), 4.79 (s, 4H), 3.78 (s, 3H),
2H-isoindole-2- 1.47 (d, 7 = 6.9 Hz, 3H)
carboxamide
N-(4-{ [(2R)-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) amino-4-methyl- 1 - δ 7.93 - 7.76 (m, 2H), 7.76 - 7.52 (m, 2H), m/e 395 oxopentan-2- 7.46 - 7.19 (m, 4H), 4.80 (s, 4H), 4.62 - 4.39 (M+H)+
1316 yl]carbamoyl}phenyl (m, 1H), 1.78 - 1.50 (m, 3H), 0.92 (dd, 7 =
)-l,3-dihydro-2H- 11.0, 6.1 Hz, 6H)
isoindole-2- carboxamide
N-(4-{ [l-(3,5- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) dimethyl-lH- δ 7.80 - 7.67 (m, 2H), 7.66 - 7.56 (m, 2H), m/e 418 pyrazol- 1 -yl)propan- 7.48 - 7.09 (m, 4H), 4.79 (s, 4H), 4.38 (h, 7 (M+H)+ 2- = 6.6 Hz, 1H), 4.22 - 4.00 (m, 2H), 2.25 (s,
1317
yl]carbamoyl}phenyl 3H), 2.14 (s, 3H), 1.16 (d, 7 = 6.8 Hz, 3H)
)-l,3-dihydro-2H- isoindole-2- carboxamide
N-{4-[(2,2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) difluoroethyl)carbam δ 7.93 - 7.72 (m, 2H), 7.73 - 7.57 (m, 2H), m/e 346 oyl]phenyl}-l,3- 7.44 - 7.22 (m, 4H), 6.28 - 5.80 (m, 1H), (M+H)+
1318
dihydro-2H- 4.79 (s, 4H), 3.78 - 3.55 (m, 2H)
isoindole-2- carboxamide N-(4-{ [2-(tetrahydro- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
2H-pyran-4- δ 7.81 - 7.68 (m, 2H), 7.68 - 7.53 (m, 2H), m/e 394 yl)ethyl]carbamoyl}p 7.44 - 7.25 (m, 4H), 4.79 (s, 4H), 3.93 - 3.74 (M+H)+
1319
henyl) - 1 , 3 - dihydro - (m, 2H), 3.34 - 3.30 (m, 2H), 1.73 - 1.43 (m,
2H-isoindole-2- 4H), 1.35 - 1.06 (m, 2H)
carboxamide
N-{4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
[(tetrahydrofuran-2- δ 7.83 - 7.72 (m, 2H), 7.67 - 7.47 (m, 2H), m/e 366 ylmethyl)carbamoyl] 7.43 - 7.17 (m, 4H), 4.79 (s, 4H), 4.00 (p, J (M+H)+
1320
phenyl } - 1 , 3 -dihydro - = 6.2 Hz, 1H), 3.88 - 3.72 (m, 1H), 3.73 - 2H-isoindole-2- 3.55 (m, 1H), 3.34 (d, 7 = 5.9 Hz, 2H), 2.01 carboxamide - 1.76 (m, 3H), 1.71 - 1.49 (m, 1H)
N-{4-[(2-methoxy-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methylpropyl)carbam δ 7.86 - 7.71 (m, 2H), 7.71 - 7.58 (m, 2H), m/e 368 oyl]phenyl}-l,3- 7.46 - 7.22 (m, 4H), 4.79 (s, 4H), 3.35 (s, (M+H)+
1321
dihydro-2H- 2H), 3.18 (s, 3H), 1.14 (s, 6H)
isoindole-2- carboxamide
N-(4-{ [(5-methyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) l,2-oxazol-3- δ 7.81 - 7.75 (m, 2H), 7.67 - 7.61 (m, 2H), m/e 377 yl)methyl]carbamoyl 7.39 - 7.28 (m, 4H), 4.83 - 4.76 (m, 5H), (M+H)+
1322 }phenyl)-l,3- 4.46 (s, 2H), 2.36 (d, J = 0.9 Hz, 3H)
dihydro-2H- isoindole-2- carboxamide
N-(4-{ [(l-methyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) lH-pyrazol-4- δ 7.75 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 m/e 376 yl)methyl]carbamoyl Hz, 2H), 7.54 (s, 1H), 7.39 - 7.20 (m, 4H), (M+H)+
1323 }phenyl)-l,3- 4.79 (s, 4H), 4.30 (s, 2H), 3.78 (s, 3H)
dihydro-2H- isoindole-2- carboxamide
N-(4-{ [2-(3,5- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) dimethyl-lH- δ 7.83 - 7.64 (m, 2H), 7.68 - 7.53 (m, 2H), m/e 404 pyrazol-1- 7.46 - 7.13 (m, 4H), 4.79 (s, 4H), 4.13 (t, J = (M+H)+
1324 yl)ethyl]carbamoyl}p 6.5 Hz, 2H), 3.58 (t, J = 6.5 Hz, 2H), 2.19 (s,
henyl) - 1 , 3 - dihydro - 3H), 2.12 (s, 3H)
2H-isoindole-2- carboxamide
N-alpha-{4-[(l,3- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) dihydro-2H-isoindol- δ 7.70 - 7.66 (m, 2H), 7.66 - 7.56 (m, 2H), m/e 429
2- 7.39 - 7.22 (m, 8H), 7.22 - 7.12 (m, 1H), (M+H)+
1325
ylc arbonyl) amino] be 4.79 (s, 4H), 4.72 - 4.62 (m, 1H), 3.20 - 3.11 nzoyl}-L- (m, 1H), 3.08 - 2.91 (m, 1H)
phenylalaninamide
N-(4-{ [2-(2-methyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) l,3-thiazol-4- δ 7.74 (dd, J = 6.8, 1.8 Hz, 2H), 7.70 - 7.57 m/e 477 yl)ethyl]carbamoyl}p (m, 2H), 7.43 - 7.23 (m, 4H), 7.19 - 6.98 (m, (M+H)+
1326
henyl) - 1 , 3 - dihydro - 1H), 4.80 (s, 4H), 3.66 - 3.41 (m, 2H), 3.05
2H-isoindole-2- - 2.85 (m, 2H), 2.65 (d, J = 5.2 Hz, 3H)
carboxamide
N-(4-{ [(2S)-3,3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
1327 dimethyl-1- δ 7.87 - 7.69 (m, 2H), 7.69 - 7.49 (m, 2H), m/e 409 (methylamino) - 1 - 7.49 - 7.24 (m, 4H), 4.80 (s, 4H), 4.45 - 4.33 (M+H)+ oxobutan-2- (m, 1H), 2.66 (d, J = 20.0 Hz, 3H), 1.02 (d, 7
yl]carbamoyl}phenyl = 18.5 Hz, 9H)
)-l,3-dihydro-2H- isoindole-2- carboxamide
N-[4-(thiophen-3- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) ylcarbamoyl)phenyl] δ 7.97 - 7.82 (m, 2H), 7.75 - 7.61 (m, 3H), m/e 364
1328 -l,3-dihydro-2H- 7.46 - 7.24 (m, 5H), 4.81 (s, 4H) (M+H)+ isoindole-2- carboxamide
N-(4-{ [2-(5-methyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) lH-pyrazol-1- δ 7.80 - 7.67 (m, 2H), 7.67 - 7.55 (m, 2H), m/e 390 yl)ethyl]carbamoyl}p 7.45 - 7.20 (m, 5H), 6.00 (dd, J = 5.0, 0.7 (M+H)+
1329
henyl) - 1 , 3 - dihydro - Hz, 1H), 4.79 (s, 4H), 4.21 (t, 7 = 6.6 Hz,
2H-isoindole-2- 2H), 3.61 (t, 7 = 6.6 Hz, 2H), 2.25 (s, 3H)
carboxamide
N-(4-{ [2-(3-methyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) lH-pyrazol-1- δ 7.76 - 7.68 (m, 2H), 7.68 - 7.52 (m, 2H), m/e 390 yl)ethyl]carbamoyl}p 7.56 - 7.42 (m, 1H), 7.44 - 7.24 (m, 4H), (M+H)+
1330
henyl) - 1 , 3 - dihydro - 5.99 (d, 7 = 2.1 Hz, 1H), 4.79 (s, 4H), 4.21
2H-isoindole-2- (t, J = 6.4 Hz, 2H), 3.63 (t, J = 6.4 Hz, 2H), carboxamide 2.21 (d, 7 = 33.1 Hz, 3H)
N-{4-[(2S)-butan-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) ylcarbamoyl]phenyl } δ 7.88 - 7.68 (m, 2H), 7.66 - 7.49 (m, 2H), m/e 338
1331 -l,3-dihydro-2H- 7.44 - 7.19 (m, 4H), 4.79 (s, 4H), 4.01 - 3.80 (M+H)+ isoindole-2- (m, 1H), 1.70 - 1.33 (m, 2H), 1.16 (d, 7 = 6.6 carboxamide Hz, 3H), 0.88 (t, 7 = 7.4 Hz, 3H)
N-{4-[(3,3-dimethyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) 2- δ 7.88 - 7.69 (m, 2H), 7.72 - 7.54 (m, 2H), m/e 380 oxobutyl)carbamoyl] 7.47 - 7.19 (m, 4H), 4.80 (s, 4H), 4.30 (s, (M+H)+
1332
phenyl } - 1 , 3 -dihydro - 2H), 1.18 (s, 9H)
2H-isoindole-2- carboxamide
N-(4-{ [(l-methyl- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) lH-pyrazol-3- δ 7.83 - 7.73 (m, 2H), 7.70 - 7.59 (m, 2H), m/e 376 yl)methyl]carbamoyl 7.55 - 7.46 (m, 1H), 7.41 - 7.22 (m, 4H), (M+H)+
1333 }phenyl)-l,3- 6.15 (d, 7 = 2.2 Hz, 1H), 4.79 (s, 4H), 4.42
dihydro-2H- (s, 2H)
isoindole-2- carboxamide
N-(4-{ [2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
(acetylamino)phenyl] δ 7.90 - 7.79 (m, 2H), 7.76 - 7.66 (m, 3H), m/e 415 carbamoyl jphenyl)- 7.51 - 7.42 (m, 1H), 7.41 - 7.26 (m, 4H), (M+H)+
1334
l,3-dihydro-2H- 7.26 - 7.13 (m, 2H), 4.85 - 4.77 (m, 4H),
isoindole-2- 2.14 - 2.05 (m, 3H)
carboxamide
N-{4-[(l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methoxybutan-2- δ 7.83 - 7.70 (m, 2H), 7.70 - 7.55 (m, 2H), m/e 368 yl)carbamoyl]phenyl 7.45 - 7.23 (m, 4H), 4.79 (s, 4H), 4.16 - 3.89 (M+H)+
1335
}-l,3-dihydro-2H- (m, 1H), 3.52 - 3.33 (m, 2H), 1.75 - 1.42 (m, isoindole-2- 2H), 0.90 (t, 7 = 7.4 Hz, 3H)
carboxamide N-[4-(tetrahydro-2H- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) pyran-4- δ 7.85 - 7.71 (m, 2H), 7.66 - 7.53 (m, 2H), m/e 366 ylcarbamoyl)phenyl] 7.48 - 7.20 (m, 4H), 4.79 (s, 4H), 4.05 - 3.82 (M+H)+
1336
-l,3-dihydro-2H- (m, 3H), 3.48 - 3.31 (m, 2H), 1.93 - 1.70 (m, isoindole-2- 2H), 1.70 - 1.48 (m, 2H)
carboxamide
N-[4-(pyrimidin-4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) ylcarbamoyl)phenyl] δ 8.93 - 8.85 (m, 1H), 8.72 - 8.62 (m, 1H), m/e 359
1337 -l,3-dihydro-2H- 8.21 - 8.11 (m, 1H), 8.03 - 7.91 (m, 2H), (M+H)+ isoindole-2- 7.77 - 7.66 (m, 2H), 7.42 - 7.26 (m, 4H),
carboxamide 4.81 (d, 7 = 5.2 Hz, 4H)
N-(4-{ [2-(lH-pyrrol- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) 1- δ 7.78 - 7.66 (m, 2H), 7.66 - 7.57 (m, 2H), m/e 375 yl)ethyl]carbamoyl}p 7.37 - 7.26 (m, 4H), 6.87 - 6.56 (m, 1H), (M+H)+
1338
henyl) - 1 , 3 - dihydro - 6.10 - 5.80 (m, 1H), 4.79 (s, 4H), 4.08 (t, J =
2H-isoindole-2- 6.5 Hz, 2H), 3.70 - 3.48 (m, 2H)
carboxamide
N-(4-{ [(2S)-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methylbutyl]carbamo δ 7.83 - 7.70 (m, 2H), 7.70 - 7.52 (m, 2H), m/e 352 yl } phenyl) -1,3 - 7.45 - 7.17 (m, 4H), 4.79 (s, 4H), 3.24 - 3.16 (M+H)+
1339
dihydro-2H- (m, 1H), 3.16 - 2.98 (m, 1H), 1.77 - 1.55 (m, isoindole-2- 1H), 1.51 - 1.31 (m, 1H), 1.31 - 1.01 (m,
carboxamide 1H), 0.90 (dd, J = 13.5, 6.4 Hz, 6H)
N-{4-[(l-amino-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) oxohexan-2- δ 7.86 - 7.70 (m, 3H), 7.68 - 7.47 (m, 3H), m/e 395 yl)carbamoyl]phenyl 7.47 - 6.53 (m, 6H), 4.84 - 4.32 (m, 7H), (M+H)+
1340
}-l,3-dihydro-2H- 3.27 (s, 73H), 2.61 - 2.29 (m, 11H), 2.04 - isoindole-2- 1.61 (m, 3H), 1.56 - 0.69 (m, 10H), 0.18 - - carboxamide 0.03 (m, 2H)
N-{4-[(2-amino-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) oxo-1- δ 7.86 - 7.73 (m, 2H), 7.84 - 7.78 (m, 2H), m/e 315 phenylethyl)c arb amo 7.70 - 7.57 (m, 2H), 7.68 - 7.62 (m, 2H), (M+H)+
1341 yl] phenyl} -1,3 - 7.53 - 7.49 (m, 1H), 7.51 (dd, 7 = 6.8, 5.5
dihydro-2H- Hz, 2H), 7.40 - 7.26 (m, 7H), 7.36 - 7.22
isoindole-2- (m, 5H), 5.63 (s, 1H), 5.63 (s, 1H), 4.79 (s, carboxamide 4H), 4.79 (s, 4H)
N-{4-[(3-tert- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) butoxypropyl)carbam δ 7.80 - 7.68 (m, 2H), 7.68 - 7.53 (m, 2H), m/e 396 oyl]phenyl}-l,3- 7.37 - 7.18 (m, 4H), 4.79 (s, 4H), 3.44 - 3.29 (M+H)+
1342
dihydro-2H- (m, 4H), 1.81 - 1.62 (m, 2H), 1.15 (s, 9H)
isoindole-2- carboxamide
N-(4-{ [3- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
(methylcarb amoyl)ph δ 7.97 - 7.85 (m, 3H), 7.76 - 7.65 (m, 2H), m/e 415 enyl]carbamoyl }phe 7.45 - 7.26 (m, 6H), 4.85 - 4.77 (m, 4H), (M+H)+
1343
nyl)-l,3-dihydro-2H- 2.86 - 2.78 (m, 3H)
isoindole-2- carboxamide
N-(4-{ [(2R)-3- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methylbutan-2- δ 7.90 - 7.68 (m, 2H), 7.66 - 7.56 (m, 2H), m/e 352 yl]carbamoyl}phenyl 7.40 - 7.17 (m, 4H), 4.79 (s, 4H), 4.02 - 3.72 (M+H)+
1344
)-l,3-dihydro-2H- (m, 1H), 1.94 - 1.65 (m, 1H), 1.12 (d, 7 = 6.7 isoindole-2- Hz, 3H), 0.90 (d, 7 = 6.8 Hz, 6H)
carboxamide N-(4-{ [(2S)-3- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+)) methylbutan-2- δ 7.85 - 7.68 (m, 2H), 7.67 - 7.51 (m, 2H), m/e 352 yl]carbamoyl}phenyl 7.48 - 7.11 (m, 4H), 4.79 (s, 4H), 3.95 - 3.74 (M+H)+
1345
)-l,3-dihydro-2H- (m, 1H), 1.92 - 1.64 (m, 1H), 1.12 (d, 7 = 6.8 isoindole-2- Hz, 3H), 1.00 - 0.79 (m, 6H)
carboxamide
N-(4-{ [2-methyl-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) (ESI(+))
(morpholin-4- δ 7.83 - 7.70 (m, 2H), 7.70 - 7.52 (m, 2H), m/e 423 yl)propan-2- 7.45 - 7.17 (m, 4H), 4.79 (s, 4H), 3.24 - 3.16 (M+H)+
1346 yl]carbamoyl}phenyl (m, 1H), 3.16 - 2.98 (m, 1H), 1.77 - 1.55 (m,
)-l,3-dihydro-2H- 1H), 1.51 - 1.31 (m, 1H), 1.31 - 1.01 (m,
isoindole-2- 1H), 0.90 (dd, J = 13.5, 6.4 Hz, 6H)
carboxamide
N-(4-{ [2-methyl-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+))
(morpholin-4- δ 7.91 - 7.75 (m, 2H), 7.75 - 7.60 (m, 2H), m/e 423 yl)propyl] carbamoyl 7.44 - 7.23 (m, 4H), 4.80 (s, 4H), 4.01 - 3.86 (M+H)+
1348 }phenyl)-l,3- (m, 4H), 3.63 (s, 2H), 3.50 - 3.35 (m, 4H),
dihydro-2H- 1.38 (s, 6H)
isoindole-2- carboxamide
N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) (ESI(+)) ethoxypropyl)carbam δ 7.84 - 7.70 (m, 2H), 7.70 - 7.55 (m, 2H), m/e 368 oyl]phenyl}-l,3- 7.43 - 7.24 (m, 4H), 4.79 (s, 4H), 3.72 - 3.55 (M+H)+
1349
dihydro-2H- (m, 1H), 3.58 - 3.44 (m, 2H), 3.38 - 3.31 (m, isoindole-2- 1H), 1.20 - 1.01 (m, 6H)
carboxamide
Example 132
N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxarnide A solution of 5-cyano-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide (30 mg, 0.9 mmol) in sulfuric acid (0.1 mL) and trifluoroacetic acid (0.3 mL) was stirred at room temperature for 16 hours. The reaction was treated with ice and the suspension was stirred for 10 minutes and filtered. The solid collected was washed with water and dried under vacuum; the solid was purified by reverse-phase HPLC to provide the title compound. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.61 (s, 1H), 8.26 (t, J = 5.7 Hz, 1H), 7.97-8.00 (bs, 1H), 7.81-7.86 (m, 2H), 7.75-7.79 (m, 2H), 7.63-7.68 (m, 2H), 7.44 (d, J = 7.8 Hz, 1H), 7.34-7.39 (bs, 1H), 4.81-4.82 (bs, 4H), 3.16-3.24 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, J = 7.4 Hz, 3H); MS (ESI(+)) m/e 367 (M+H)+.
Example 272
methyl 2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylate
Example 272A
4-amino-N-propylbenzamide
5-amino-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide A solution of 4-nitro-N-propylbenzamide (800 mg, 0.1 mmol) in 40 ml
tetrahydrofuran in the presence of 160 mg of 20% Pd on carbon was treated in a pressure bottle with 30 psi of hydrogen for 30 minutes at room temperature. The suspension was filtered through a nylon membrane and concentrated to provide the title compound.
Example 272B
methyl 2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylate A solution of 4-amino-N-propylbenzamide (390 mg, 2.19 mmol), bis(2,5- dioxopyrrolidin-l-yl) carbonate (700 mg, 2.74 mmol), and pyridine (0.18 mL, 2.19 mmol) in acetonitrile (5 mL) was stirred at ambient temperature for 30 minutes. Diisopropylethylamine (0.85 mL, 6.6 mmol)) was added followed by a suspension of methyl isoindoline-5- carboxylate hydrochloride (538 mg, 2.52 mmol) and diisopropylethylamine (0.46 mL, 4.4 mmol) in l-methyl-2-pyrrolidinone (8 mL) added dropwise via syringe over ~5 minutes. The reaction became a suspension and was stirred 3 hours. The reaction was treated with water (30 mL) and the resulting suspension was stirred 5 minutes and filtered. The solid collected was washed with water and dried under vacuum to provide the title compound. ¾ NMR (300 MHz, DMSO-de) δ ppm 8.63 (s, 1H), 8.26 (t, J = 5.6 Hz, 1H), 7.94-7.97 (m, 1H), 7.90-7.96 (m, 1H), 7.75-7.78 (m, 2H), 7.63-7.67 (m, 2H), 7.52 (d, 7 = 7.9 Hz, 1H), 4.83-4.86 (m, 4H), 3.87 (s, 3H), 3.16-3.22 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 382 (M+H)+.
Example 273
2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid The title compound was prepared as described in Example IB, substituting methyl 2-
{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylate for methyl 4- (isoindoline-2-carboxamido)benzoate. ¾ NMR (300 MHz, DMSO-<¾ δ ppm 12.90-13.07 (bs, 1H), 8.62 (s, 1H), 8.26 (t, 7 = 5.7 Hz, 1H), 7.88-7.93 (m, 2H), 7.75-7.78 (m, 2H), 7.63- 7.67 (m, 2H), 7.49 (d, 7 = 7.9 Hz, 1H), 4.83-4.85 (bs, 4H), 3.16-3.24 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); (ESI(+)) m/e 368 (M+H)+.
Example 274
5-amino-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide A solution of 5-nitro-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide (37 mg, 0.1 mmol) in 1 ml dimethylformamide in the presence of 11 mg of 10% Pd on carbon was treated with a hydrogen balloon overnight at room temperature. The suspension was filtered through diatomaceous earth and purified by reverse-phase HPLC to provide the title compound. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.51 (s, 1H), 8.24 (t, 7 = 5.6 Hz, 1H), 7.74-7.78 (m, 2H), Ί .62-1.66 (m, 2H), 7.19 (d, 7 = 7.9 Hz, 1H), 6.78-6.89 (m, 2H), 4.67-4.71 (m, 4H), 3.15-3.26 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 339 (M+H)+. Example 275
5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide A solution of calcium chloride (0.031 g, 0.277 mmol) in ethanol (0.8 mL) was added to a suspension of methyl 2-(4-(propylcarbamoyl)phenylcarbamoyl)isoindoline-5-carboxylate (0.04 g, 0.105 mmol) in tetrahydrofuran (1 mL). Sodium borohydride (0.02 g, 0.524 mmol) was then added in one portion and the suspension stirred at room temperature. After 18 hours, the mixture was concentrated to remove tetrahydrofuran then saturated aqueous sodium bicarbonate and water was added. The suspension was filtered and the solid was flash chromatographed to provide the title compound. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.55 (s, 1H), 8.25 (t, 7 = 5.6 Hz, 1H), 7.74-7.78 (m, 2H), 7.64-7.67 (m, 2H), 7.31 (d, 7 = 4.0 Hz,
1H), 7.30 (d, 7 = 2.3 Hz, 1H), 7.26 (d, 7 = 8.0 Hz, 1H), 5.19 (t, 7 = 5.6 Hz, 1H), 4.71-4.78 (m, 4H), 4.52 (d, 7 = 5.4 Hz, 2H), 3.15-3.25 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 354 (M+H)+.
Example 276
5-(aminomemyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxamide 5-Cyano-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide (0.04 g, 0.115 mmol) and 7M ammonia-methanol/tetrahydrofuran /methanol (4 mL) were added to Ra-Ni 2800, water slurry (0.080 g, 1.363 mmol) in a 50 ml pressure bottle and stirred for 16 hours at 30 psi and room temperature. The mixture was filtered through a nylon membrane, concentrated and purified by reverse-phase HPLC to provide the title compound. ¾ NMR (300 MHz, Methanol-^) δ ppm 7.76-7.79 (m, 2H), 7.60-7.63 (m, 2H), 7.31-7.35 (m, 3H), 4.82 (s, 4H), 3.86 (s, 2H), 3.30-3.33 (m, 2H), 1.53-1.75 (m, 2H), 0.98 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 425 (M+H)+.
Example 277
5-[(2-hydroxy-2-memylpropanoyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting 5-amino- N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide for 3-phenylpropan-l-amine and 2-hydroxy-2-methylpropanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.59 (s, 1H), 8.55 (s, 1H), 8.25 (t, 7 = 5.7 Hz, 1H), 7.81 (s, 1H), 7.74-7.78 (m, 2H), 7.62-7.68 (m, 2H), 7.59-7.64 (m, 1H), 7.28 (d, 7 = 8.3 Hz, 1H), 5.71-5.75 (m, 1H), 4.72-4.80 (m, 4H), 3.16-3.23 (m, 2H), 1.42-1.59 (m, 2H), 1.36 (s, 6H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 425 (M+H)+.
Example 278
5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide A solution of 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide (0.035 g, 0.103 mmol) in dimethylformamide (0.7 mL) was treated with N,N- diisopropylethylamine (0.018 mL, 0.103 mmol) followed by acetyl chloride (0.011 g, 0.134 mmol) and the reaction solution was stirred at room temperature for 16 hours. The reaction was concentrated and purified by reverse-phase HPLC to provide the title compound. ¾
NMR (300 MHz, DMSO- ) δ ppm 9.97 (s, IH), 8.52 (s, IH), 8.25 (t, J = 5.7 Hz, IH), 7.74- 7.78 (m, 2H), 7.65-7.67 (m, IH), 7.62-7.67 (m, 2H), 7.43 (dd, 7 = 8.2, 1.9 Hz, IH), 7.27 (d, 7 = 8.2 Hz, IH), 4.71-4.76 (m, 4H), 3.16-3.21 (m, 2H), 2.04 (s, 3H), 1.46-1.59 (m, 2H), 0.89 (t, J = 1.4 Hz, 3H); MS (ESI(+)) m/e 381 (M+H)+.
Example 279
5-[(N,N-dimethylglycyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting 5-amino- N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide for 3-phenylpropan-l-amine and 2-(dimethylamino)acetic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.76 (s, IH), 8.54 (s, IH), 8.25 (t, 7 = 5.6 Hz, IH), 7.74-7.78 (m, 2H), 7.73 (d, 7 = 1.8 Hz, IH), 7.63-7.67 (m, 2H), 7.54 (dd, 7 = 8.2, 1.9 Hz, IH), 7.28 (d, 7 = 8.2 Hz, IH), 4.72-4.76 (m, 4H), 3.16-3.24 (m, 2H), 3.07 (s, 2H), 2.28 (s, 6H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(-)) m/e 422 (M-H)\
Example 280
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide
In a 4 mL vial, a solution of 5-bromo-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide (50 mg, 0.12 mmol) and lH-pyrazol-3-ylboronic acid (17 mg, 0.15 mmol) in dimethylformamide was treated with saturated aqueous sodium bicarbonate followed by bis(triphenylphosphine)palladium(II) chloride (7 mg). The vial was capped under nitrogen and the reaction heated at 85 °C for 6 hours. The reaction was cooled to ambient temperature and water was added. The resulting suspension was stirred for 5 minutes and filtered. The solid collected was washed with water and dried under vacuum; the solid was purified by reverse- phase HPLC to provide the title compound. ¾ NMR (300 MHz, DMSO- ) δ ppm 12.39-13.18 (bs, IH), 8.59 (s, IH), 8.24-8.28 (m, IH), 7.75-7.79 (m, 2H), 7.70-7.80 (m, 3H), 7.62-7.69 (m, 2H), 7.40 (d, 7 = 1.9 Hz, IH), 6.73 (d, 7 = 2.2 Hz, IH), 4.79-4.83 (m, 4H), 3.15- 3.25 (m, 2H), 1.46-1.57 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 390 (M+H)+.
Example 281
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide The title compound was prepared as described in Example 280, substituting 4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 10.91-13.69 (bs, 1H), 8.58 (s, 1H), 8.26 (t, J = 5.7 Hz, 1H), 8.07-8.08 (bs, 2H), 7.75-7.79 (m, 2H), 7.67 (s, 1H), 7.54-7.65 (m, 2H), 7.57 (d, 7 = 7.8 Hz, 1H), 7.34 (d, 7 = 7.8 Hz, 1H), 4.76-4.79 (m, 4H), 3.15-3.25 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 390 (M+H)+.
Example 282
5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting 2- methoxyacetyl chloride for acetyl chloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.80 (s, 1H), 8.54 (s, 1H), 8.25 (t, 7 = 5.7 Hz, 1H), 7.74-7.79 (m, 2H), 7.72-7.74 (m, 1H), 7.63-7.67 (m, 2H), 7.55 (dd, 7 = 8.2, 1.9 Hz, 1H), 7.30 (d, 7 = 8.2 Hz, 1H), 4.72-4.77 (m, 4H), 4.00 (s, 2H), 3.38 (s, 3H), 3.17-3.19 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 411 (M+H)+.
Example 283
5- [(methylsulfonyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide
A solution of 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide (0.035 g, 0.103 mmol), pyridine (0.017 mL, 0.207 mmol) and catalytic N,N- dimethylaminopyridine in dimethylformamide (0.7 mL) was cooled to 0 °C. Methanesulfonyl chloride (0.014 g, 0.126 mmol) was added and the reaction solution was allowed to stir at room temperature for 2 hours. The reaction mixture was concentrated and purified by reverse- phase HPLC to provide the title compound. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.74 (s, 1H), 8.54 (s, 1H), 8.26 (t, 7 = 5.6 Hz, 1H), 7.74-7.78 (m, 2H), 7.63-7.66 (m, 2H), 7.32 (d, 7 = 8.1 Hz, 1H), 7.14-7.20 (m, 2H), 4.73-4.76 (m, 4H), 3.15-3.25 (m, 2H), 2.98 (s, 3H), 1.45-1.62 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 417 (M+H)+.
Table 4.
The following Examples were prepared essentially as described in Example 1, substituting l,3-dihydro-2H-pyrrolo[3,4-c]pyridine, 5,7-dihydro-6H-pyrrolo[3,4-b]pyridine, or 6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine for isoindoline in Example 1A and using an appropriate amine as described in Example 1C. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC; some compounds also required Boc-deprotection after amide coupling as described in Example 2D. Accordingly, some Examples were isolated as trifluoroacetic acid salts.
Figure imgf000714_0001
dimethoxybenzyl)carb Hz, IH), 8.66 (s, IH), 8.61 (s, IH), 8.50 (d, J = 5.0 Hz, m/e 433 amoyl] pheny 1 } - 1 , 3 - IH), 7.80-7.84 (m, 2H), 7.65-7.69 (m, 2H), 7.44 (d, 7 (M+H)+ dihydro-2H- = 5.1 Hz, IH), 6.48 (d, 7 = 2.3 Hz, 2H), 6.37 (t, 7 = 2.3 pyrrolo[3,4-c]pyridine- Hz, IH), 4.81-4.85 (m, 4H), 4.39 (d, 7 = 5.9 Hz, 2H),
2-carboxamide 3.31 (s, 6H)
286 N-{4-[(4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.88 (t, 7 = 6.0 (ESI(+)) chlorobenzyl)carbamo Hz, IH), 8.66 (s, IH), 8.61 (s, IH), 8.50 (d, 7 = 5.0 Hz, m/e 407 yl]phenyl}-l,3- IH), 7.80-7.84 (m, 2H), 7.65-7 '.69 (m, 2H), 7.32-7.45 (M+H)+ dihydro-2H- (m, 5H), 4.78-4.88 (m, 4H), 4.44 (d, 7 = 5.9 Hz, 2H) pyrrolo[3,4-c]pyridine-
2-carboxamide
287 N-(4-{ [4-(pyridin-2- ¾ NMR (300 MHz, DMSO-<¾ δ ppm 8.61-8.64 (m, (ESI(+)) yl)piperazin-l- 2H), 8.51 (d, 7 = 5.0 Hz, IH), 8.13 (ddd, 7 = 4.9, 2.0, m/e 429 yl] c arbonyl } phenyl) - 0.8 Hz, IH), 7.64-7.68 (m, 2H), 7.56 (ddd, 7 = 8.7, (M+H)+ l,3-dihydro-2H- 7.0, 1.9 Hz, IH), 7.44 (d, 7 = 5.1 Hz, IH), 7.36-7.40
pyrrolo[3,4-c]pyridine- (m, 2H), 6.85 (d, 7 = 8.6 Hz, IH), 6.65-6.69 (m, IH),
2-carboxamide 4.81-4.85 (m, 4H), 3.53-3.63 (m, 8H)
288 N-{4-[(3- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.61-8.64 (m, (ESI(+)) phenylpropyl)carbamo 2H), 8.50 (d, 7 = 5.0 Hz, IH), 8.27-8.31 (m, IH), 7.75- m/e 401 yl]phenyl}-l,3- 7.79 (m, 2H), 7.63-7.67 (m, 2H), 7.44 (d, 7 = 5.1 Hz, (M+H)+ dihydro-2H- IH), 7.15-7.31 (m, 5H), 4.76-4.89 (m, 4H), 3.20-3.32 pyrrolo[3,4-c]pyridine- (m, 2H), 2.63 (t, 7 = 7.6 Hz, 2H), 1.77-1.88 (m, 2H)
2-carboxamide
289 N-{4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.65 (s, IH), (ESI(+))
[(tetrahydrofuran-3 - 8.61 (s, IH), 8.50 (d, 7 = 5.0 Hz, IH), 8.39 (t, 7 = 5.7 m/e 367 ylmethyl)c arb amoyl] p Hz, IH), 7.75-7.79 (m, 2H), 7.63-7.68 (m, 2H), 7.44 (M+H)+ henyl } - 1 ,3-dihydro- (d, 7 = 5.1 Hz, IH), 4.81-4.84 (m, 4H), 3.57-3.78 (m,
2H-pyrrolo[3,4- 3H), 3.48 (dd, 7 = 8.5, 5.3 Hz, IH), 3.14-3.30 (m, 2H), c]pyridine-2- 2.41-2.51 (m, IH), 1.87-2.12 (m, IH), 1.54-1.66 (m, carboxamide IH)
290 N-{4-[(3- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.61-8.64 (m, (ESI(+)) methylbutyl)carbamoy 2H), 8.50 (d, 7 = 5.0 Hz, IH), 8.21 (t, 7 = 5.6 Hz, IH), m/e 353 l]phenyl } - 1 ,3-dihydro- 7.74-7.78 (m, 2H), 7.62-7.66 (m, 2H), 7.44 (d, 7 = 5.1 (M+H)+ 2H-pyrrolo[3,4- Hz, IH), 4.81-4.84 (m, 4H), 3.20-3.33 (m, 2H), 1.53- c]pyridine-2- 1.69 (m, IH), 1.37-1.45 (m, 2H), 0.91 (d, 7 = 6.6 Hz, carboxamide 6H)
426 N-(4-{ [(2S)- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.65 (s, IH), (ESI(-)) tetrahydrofuran-2- 8.61 (s, IH), 8.50 (d, 7 = 5.0 Hz, IH), 8.33 (t, 7 = 5.8 m/e 367 ylmethyl]carbamoyl }p Hz, IH), 7.76-7.81 (m, 2H), 7.63-7.67 (m, 2H), 7.44 (M+H)" henyl)- 1, 3-dihydro- (d, 7 = 5.1 Hz, IH), 4.76-4.89 (m, 4H), 3.96 (p, 7 = 6.3
2H-pyrrolo[3,4- Hz, IH), 3.73-3.82 (m, IH), 3.58-3.67 (m, IH), 3.26- c]pyridine-2- 3.35 (m, 2H), 1.73-1.98 (m, 3H), 1.52-1.66 (m, IH)
carboxamide
427 N-(4-{ [(2R)- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.63-8.65 (bs, (ESI(-)) tetrahydrofuran-2- IH), 8.61-8.62 (bs, IH), 8.50 (d, 7 = 5.0 Hz, IH), 8.32 m/e 411 ylmethyl]carbamoyl }p (t, 7 = 5.8 Hz, IH), 7.76-7.81 (m, 2H), 7.63-7.67 (m, (M-H)+ henyl)- 1, 3-dihydro- 2H), 7.44 (d, 7 = 5.1 Hz, IH), 4.81-4.88 (m, 4H), 3.97
2H-pyrrolo[3,4- (p, 7 = 6.2 Hz, IH), 3.74-3.82 (m, IH), 3.58-3.66 (m, c]pyridine-2- IH), 3.26-3.32 (m, 2H), 1.74-1.96 (m, 3H), 1.53-1.64 carboxamide (m, IH) 430 N-(4-{ to¾ NMR (300 MHz, DMSO- ) δ ppm 9.10-9.12 (bs, (APCI(+) me thy lbutyl) amino] car IH), 8.83 (s, IH), 8.67 (s, IH), 8.22 (t, 7 = 5.6 Hz, ) m/e 354 bonyl } phenyl) -5,7- IH), 7.75-7.79 (m, 2H), 7.63-7.67 (m, 2H), 4.81-4.84 (M+H)+ dihydro-6H- (m, 4H), 3.20-3.34 (m, 2H), 1.53-1.69 (m, IH), 1.37- pyrrolo[3,4- 1.45 (m, 2H), 0.91 (d, 7 = 6.6 Hz, 6H)
d]pyrimidine-6- carboxamide
431 N-(4-{ [(3- ¾ NMR (300 MHz, DMSO-d6) δ ppm 9.11 (s, IH), (APCI(+) phenylpropyl) amino] c 8.83 (s, IH), 8.68 (s, IH), 8.30 (t, 7 = 5.6 Hz, IH), ) m/e 402 arbonyl}phenyl)-5,7- 7.76-7.80 (m, 2H), 7.64-7.68 (m, 2H), 7.15-7.32 (m, (M+H)+ dihydro-6H- 5H), 4.77-4.89 (m, 4H), 3.21-3.34 (m, 2H), 2.60-2.74
pyrrolo[3,4- (m, 2H), 2.29-1.90 (m, 2H)
d]pyrimidine-6- carboxamide
437 N-[4-({ [(lS)-2- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.66 (s, IH), (ESI(+)) hydroxy-1- 8.61 (s, IH), 8.51 (d, 7 = 2.0 Hz, IH), 8.49 (d, 7 = 5.2 m/e 403 phenylethyl] amino } car Hz, IH), 7.82-7.87 (m, 2H), 7.66-7 '.70 (m, 2H), 7.38- (M+H)+ bonyl)phenyl] -1,3- 7.45 (m, 3H), 7.29-7.34 (m, 2H), 7.19-7.26 (m, IH),
dihydro-2H- 5.03-5.10 (m, IH), 4.90 (t, 7 = 5.8 Hz, IH), 4.79-4.87
pyrrolo[3,4-c]pyridine- (m, 4H), 3.61-3.76 (m, 2H)
2-carboxamide
445 N-[4-({ [(lS)-2- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.68 (s, IH), (ESI(+)) hydroxy- 1 -pyridin-2- 8.62 (s, IH), 8.44-8.54 (m, 3H), 7.84-7.89 (m, 2H), m/e 404 ylethyl] amino } carbony 7.75 (td, 7 = 7.7, 1.8 Hz, IH), 7.66-7.72 (m, 2H), 7.39- (M+H)+ l)phenyl] -1,3 -dihydro - 7.45 (m, 2H), 7.26 (ddd, J = 7.5, 4.8, 1.2 Hz, IH),
2H-pyrrolo[3,4- 5.10-5.17 (m, IH), 4.90 (t, J = 6.0 Hz, IH), 4.79-4.87
c]pyridine-2- (m, 4H), 3.73-3.88 (m, 2H)
carboxamide
446 N-(4-{ to¾ NMR (300 MHz, DMSO-d6) δ ppm 8.62 (s, IH), (ESI(+)) me thy lbutyl) amino] car 8.48 (dd, J = 4.9, 1.5 Hz, IH), 8.22 (t, J = 5.6 Hz, IH), m/e 353 bonyl } phenyl) -5,7- 7.81 (dd, 7 = 7.7, 1.5 Hz, IH), 7.73-7.79 (m, 2H), (M+H)+ dihydro-6H- 7.64-7.68 (m, 2H), 7.33 (dd, 7 = 7.7, 4.9 Hz, IH),
pyrrolo[3,4-b]pyridine- 4.78-4.80 (bs, 4H), 3.21-3.33 (m, 2H), 1.61 (dp, 7 =
6-carboxamide 13.3, 6.6 Hz, IH), 1.41 (q, 7 = 7.1 Hz, 2H), 0.90 (d, 7
= 6.6 Hz, 6H)
447 N-(4- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.63 (s, IH), (ESI(+))
{ [(tetrahydrofuran-3- 8.48 (dd, 7 = 4.9, 1.5 Hz, IH), 8.39 (t, 7 = 5.7 Hz, IH), m/e 367 ylmethyl)amino]carbo 7.76-7.83 (m, 3H), 7.65-7.69 (m, 2H), 7.33 (dd, 7 = (M+H)+ nyl } phenyl) -5,7 - 7.7, 4.9 Hz, IH), 4.78-4.81 (bs, 4H), 3.57-3.82 (m,
dihydro-6H- 3H), 3.44-3.51 (m, IH), 3.17-3.28 (m, 2H), 2.42-2.50
pyrrolo[3,4-b]pyridine- (m, IH), 1.85-2.02 (m, IH), 1.54-1.68 (m, IH)
6-carboxamide
448 N-{4-[(4-pyridin-2- ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.61 (s, IH), (ESI(+)) ylpiperazin-1- 8.49 (dd, 7 = 4.9, 1.5 Hz, IH), 8.13 (dd, 7 = 5.0, 1.9 m/e 429 yl)carbonyl]phenyl } - Hz, IH), 7.81 (dd, 7 = 7.7, 1.5 Hz, IH), 7.66-7.70 (m, (M+H)+
5,7-dihydro-6H- 2H), 7.56 (ddd, 7 = 8.7, 7.0, 1.8 Hz, IH), 7.36-7.41
pyrrolo[3,4-b]pyridine- (m, 2H), 7.34 (dd, 7 = 7.7, 5.0 Hz, IH), 6.85 (d, 7 =
6-carboxamide 8.6 Hz, IH), 6.67 (dd, 7 = 6.9, 4.8 Hz, IH), 4.79-4.81
(bs, 4H), 3.43-3.75 (m, 8H)
553 N- { 4- [(tetrahydro-2H- ¾ NMR (300 MHz, DMSO-d6) δ 8.64 (s, IH), 8.61 (ESI(+)) pyran-2- (s, IH), 8.50 (d, 7 = 5.0 Hz, IH), 8.29 (t, 7 = 5.8 Hz, m/e 381 ylmethyl)carbamoyl]p IH), 7.82 - 7.75 (m, 2H), 7.68 - 7.61 (m, 2H), 7.44 (d, (M+H)+ henyl } - 1 ,3-dihydro- 7 = 5.1 Hz, IH), 4.86 - 4.79 (m, 4H), 3.87 (dd, 7 =
2H-pyrrolo[3,4- 11.3, 3.0 Hz, IH), 3.48 - 3.34 (m, 2H), 3.28 - 3.17 (m, c]pyridine-2- 2H), 1.82 - 1.72 (m, IH), 1.66 - 1.56 (m, IH), 1.56 - carboxamide 1.33 (m, 3H), 1.28 - 1.07 (m, IH)
554 N- { 4- [(tetrahydro-2H- ¾ NMR (300 MHz, DMSO-d6) δ 8.63 (d, 7 = 8.3 Hz, (ESI(+)) pyran-3- 2H), 8.50 (d, J = 5.0 Hz, IH), 8.28 (t, J = 5.7 Hz, IH), m/e 381 ylmethyl)c arb amoyl] p 7.77 (d, 7 = 8.8 Hz, 2H), 7.65 (d, 7 = 8.8 Hz, 2H), 7.44 (M+H)+ henyl } - 1 ,3-dihydro- (d, 7 = 5.0 Hz, IH), 4.83 (d, 7 = 4.3 Hz, 4H), 3.82 - 2H-pyrrolo[3,4- 3.64 (m, 2H), 3.18 - 3.04 (m, 3H), 1.78 (dd, 7 = 6.9, c]pyridine-2- 3.6 Hz, 2H), 1.58 (dd, 7 = 10.2, 6.6 Hz, IH), 1.53 - carboxamide 1.36 (m, IH), 1.31 - 1.17 (m, IH)
555 N- { 4- [(tetrahydro-2H- ¾ NMR (300 MHz, DMSO-d6) δ 8.66 - 8.59 (m, 2H), (ESI(+)) pyran-4- 8.50 (d, 7 = 5.0 Hz, IH), 8.33 - 8.25 (m, IH), 7.81 - m/e 381 ylmethyl)c arb amoyl] p 7.74 (m, 2H), 7.69 - 7.61 (m, 2H), 7.44 (d, 7 = 5.0 Hz, (M+H)+ henyl } - 1 ,3-dihydro- IH), 4.82 (bs, 4H), 3.89 - 3.79 (m, 2H), 3.24 (d, 7 =
2H-pyrrolo[3,4- 11.6 Hz, IH), 3.14 (t, 7 = 6.1 Hz, 2H), 1.86 - 1.69 (m, c]pyridine-2- IH), 1.64 - 1.54 (m, 2H), 1.27 - 1.06 (m, 3H)
carboxamide
556 N-(4-{ [(2S)-l- ¾ NMR (300 MHz, DMSO-d6) δ 8.66 - 8.59 (m, 2H), (ESI(+)) hydroxy-4- 8.50 (d, 7 = 5.0 Hz, IH), 7.83 - 7.75 (m, 3H), 7.69 - m/e 383 methylpentan-2- 7.61 (m, 2H), 7.44 (d, 7 = 5.1 Hz, IH), 4.91 - 4.80 (m, (M+H)+ yl]carbamoyl jphenyl)- 4H), 4.64 (t, 7 = 5.7 Hz, IH), 4.12 - 3.99 (m, IH),
l,3-dihydro-2H- 3.41 (d, 7 = 5.3 Hz, IH), 1.69 - 1.54 (m, IH), 1.53 - pyrrolo[3,4-c]pyridine- 1.31 (m, 2H), 0.88 (t, 7 = 6.7 Hz, 6H)
2-carboxamide
599 N-[4- ¾ NMR (300 MHz, DMSO-<¾) δ ppm 8.62 (d, 7 = 4.9 (ESI(+))
(propylcarbamoyl)phe Hz, 2H), 8.50 (d, 7 = 5.0 Hz, IH), 8.30 - 8.20 (m, IH), m/e 325 nyl]- l,3-dihydro-2H- 7.83 - 7.72 (m, 2H), 7.68 - 7.59 (m, 2H), 7.44 (d, 7 = (M+H)+ pyrrolo[3,4-c]pyridine- 5.1 Hz, IH), 4.87 - 4.77 (m, 4H), 3.22 - 3.13 (m, 2H),
2-carboxamide 1.61 - 1.45 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H)
600 N-(4-{ [(2S)- ¾ NMR (300 MHz, DMSO-d6) δ 8.63 (s, IH), 8.48 (ESI(+)) tetrahydrofuran-2- (dd, 7 = 4.9, 1.5 Hz, IH), 8.34 (t, 7 = 5.8 Hz, IH), 7.85 m/e 367 ylmethyl]carbamoyl }p - 7.75 (m, 3H), 7.70 - 7.63 (m, 2H), 7.33 (dd, 7 = 7.7, (M+H)+ henyl) - 5 , 7 -dihy dro - 4.9 Hz, IH), 4.80 (bs, 4H), 3.97 (p, 7 = 6.2 Hz, IH),
6H-pyrrolo[3,4- 3.83 - 3.72 (m, IH), 3.68 - 3.57 (m, IH), 3.28 (dd, 7 =
b]pyridine-6- 5.9, 1.7 Hz, IH), 1.98 - 1.72 (m, 3H), 1.66 - 1.51 (m, carboxamide IH)
601 N-(4-{ [(2R)- ¾ NMR (300 MHz, DMSO-d6) δ 8.62 (s, IH), 8.48 (ESI(+)) tetrahydrofuran-2- (dd, 7 = 4.9, 1.5 Hz, IH), 8.32 (t, 7 = 5.8 Hz, IH), 7.85 m/e 367 ylmethyl]carbamoyl }p - 7.75 (m, 3H), 7.70 - 7.63 (m, 2H), 7.33 (dd, 7 = 7.7, (M+H)+ henyl) - 5 , 7 -dihy dro - 4.9 Hz, IH), 4.80 (bs, 4H), 3.97 (p, 7 = 6.2 Hz, IH),
6H-pyrrolo[3,4- 3.83 - 3.72 (m, IH), 3.68 - 3.57 (m, IH), 1.98 - 1.72 b]pyridine-6- (m, 3H), 1.69 - 1.51 (m, IH)
carboxamide
602 N-(4-{ [(2S)-l- ¾ NMR (300 MHz, DMSO-d6) δ 8.61 (s, IH), 8.48 (ESI(+)) hydroxy-4- (dd, 7 = 4.9, 1.5 Hz, IH), 7.87 - 7.71 (m, 4H), 7.70 - m/e 383 methylpentan-2- 7.63 (m, 2H), 7.33 (dd, 7 = 7.7, 4.9 Hz, IH), 4.79 (bs, (M+H)+ yl]carbamoyl jphenyl)- 4H), 4.13 - 3.95 (m, IH), 3.42 (dd, 7 = 10.6, 5.4 Hz,
5,7-dihydro-6H- 2H), 1.72 - 1.54 (m, IH), 1.53 - 1.31 (m, 2H), 0.88 (t, pyrrolo[3,4-b]pyridine- 7 = 6.7 Hz, 6H)
6-carboxamide
603 N-(4-{ [(lS)-2- ¾ NMR (300 MHz, DMSO-d6) δ 8.64 (s, IH), 8.53 - (ESI(+)) hydroxy-1- 8.45 (m, 2H), 7.88 - 7.78 (m, 3H), 7.73 - 7.66 (m, m/e 403 phenylethyl] carbamoyl 2H), 7.47 - 7.27 (m, 5H), 7.27 - 7.18 (m, IH), 5.12 - (M+H)+ }phenyl)-5,7-dihydro- 5.01 (m, IH), 4.90 (t, 7 = 5.8 Hz, IH), 4.80 (bs, 4H), 6H-pyrrolo[3,4- 3.78 - 3.59 (m, 2H)
b]pyridine-6- carboxamide
604 N- { 4- [(tetrahydro-2H- ¾ NMR (300 MHz, DMSO-d6) δ 8.62 (s, IH), 8.48 (ESI(+)) pyran-4- (dd, 7 = 4.9, 1.5 Hz, IH), 8.30 (t, 7 = 5.8 Hz, IH), 7.85 m/e 381 ylmethyl)c arb amoyl] p - 7.74 (m, 3H), 7.70 - 7.63 (m, 2H), 7.33 (dd, 7 = 7.7, (M+H)+ henyl } -5 ,7 -dihydro- 4.9 Hz, IH), 4.79 (bs, 4H), 3.89 - 3.79 (m, 2H), 3.28 - 6H-pyrrolo[3,4- 3.19 (m, 2H), 3.14 (t, 7 = 6.3 Hz, 2H), 1.87 - 1.70 (m, b]pyridine-6- IH), 1.64 - 1.54 (m, 2H), 1.29 - 1.01 (m, 2H)
carboxamide
613 N-(4-{ [(lS)-2- ¾ NMR (300 MHz, DMSO-d6) δ 8.65 (s, IH), 8.55 - (ESI(+)) hydroxy- 1 -(pyridin-2- 8.51 (m, IH), 8.47 (t, 7 = 6.7 Hz, 2H), 7.87 (d, 7 = 8.8 m/e 404 yl)ethyl] carbamoyl } ph Hz, 2H), 7.84 - 7.79 (m, IH), 7.76 (dd, 7 = 7.7, 1.8 (M+H)+ enyl) -5,7 -dihydro-6H- Hz, IH), 7.71 (t, 7 = 5.4 Hz, 2H), 7.41 (d, 7 = 7.8 Hz, pyrrolo[3,4-b]pyridine- IH), 7.33 (dd, 7 = 7.7, 4.9 Hz, IH), 7.29 - 7.22 (m,
6-carboxamide IH), 5.19 - 5.09 (m, IH), 4.90 (t, 7 = 5.9 Hz, IH),
4.80 (bs, 4H), 3.90 - 3.72 (m, 2H)
627 N-{4-[(4- ¾ NMR (300 MHz, DMSO- ) δ 8.60 (d, 7 = 5.9 Hz, (ESI(+)) hydroxypiperidin- 1 - 2H), 8.50 (d, 7 = 5.0 Hz, IH), 7.62 (d, 2H), 7.44 (d, 7 m/e 367 yl)carbonyl]phenyl } - = 5.1 Hz, IH), 7.30 (d, 2H), 4.82 (d, 7 = 4.3 Hz, 4H), (M+H)+ l,3-dihydro-2H- 4.76 (d, 7 = 4.0 Hz, IH), 3.73 (td, 7 = 8.3, 4.2 Hz, 2H), pyrrolo[3,4-c]pyridine- 3.22 - 3.08 (m, 2H), 1.82 - 1.65 (m, 2H), 1.43 - 1.26
2-carboxamide (m, 2H)
628 N-{4-[(2-hydroxy-2- ¾ NMR (300 MHz, DMSO- ) δ 8.64 (d, 7 = 12.5 (ESI(+)) methylpropyl)carbamo Hz, 2H), 8.50 (d, 7 = 5.0 Hz, IH), 8.06 (t, 7 = 6.0 Hz, m/e 355 yl]phenyl}-l,3- IH), 7.80 (d, 7 = 8.8 Hz, 2H), 7.66 (d, 7 = 8.8 Hz, 2H), (M+H)+ dihydro-2H- 7.44 (d, 7 = 5.1 Hz, IH), 4.83 (d, 7 = 4.3 Hz, 4H), 4.56 pyrrolo[3,4-c]pyridine- (s, IH), 3.24 (d, 7 = 6.0 Hz, 2H), 2.89 (s, IH), 1.10 (s,
2-carboxamide 6H)
629 N-{4-[(4- ¾ NMR (300 MHz, DMSO- ) δ 8.62 (d, 7 = 6.4 Hz, (ESI(+)) hydroxybutyl)carbamo IH), 8.50 (d, 7 = 5.0 Hz, IH), 8.26 (t, 7 = 5.6 Hz, IH), m/e 355 yl]phenyl}-l,3- 7.76 (d, 7 = 8.8 Hz, IH), 7.64 (d, 7 = 8.8 Hz, IH), 7.44 (M+H)+ dihydro-2H- (d, 7 = 5.1 Hz, IH), 4.82 (d, 7 = 4.3 Hz, IH), 4.39 (t, 7
pyrrolo[3,4-c]pyridine- = 5.1 Hz, IH), 3.41 (q, 7 = 6.1 Hz, IH), 3.25 - 3.15
2-carboxamide (m, 2H), 1.59 - 1.38 (m, 4H)
630 N-(4-{ [(2S)-l- ¾ NMR (300 MHz, DMSO- ) δ 8.62 (d, 7 = 6.0 Hz, (ESI(+)) hydroxy-3- 2H), 8.50 (d, 7 = 5.0 Hz, IH), 7.83 - 7.77 (m, 2H), m/e 369 methylbutan-2- 7.74 (d, 7 = 8.9 Hz, IH), 7.64 (d, 7 = 1.8 Hz, IH), 7.44 (M+H)+ yl]carbamoyl jphenyl)- (d, 7 = 5.1 Hz, IH), 4.83 (d, 7 = 4.3 Hz, 4H), 4.53 (t, 7
l,3-dihydro-2H- = 5.6 Hz, IH), 3.90 - 3.70 (m, IH), 3.51 (t, 7 = 5.8 Hz, pyrrolo[3,4-c]pyridine- 2H), 1.92 (dq, 7 = 13.6, 6.8 Hz, IH), 0.89 (dd, 7 = 7.9,
2-carboxamide 6.9 Hz, 6H)
631 N-{4-[(l-hydroxy-2- ¾ NMR (300 MHz, DMSO- ) δ 8.62 (d, 7 = 4.0 Hz, (ESI(+)) methylpropan-2- IH), 8.50 (d, 7 = 5.0 Hz, IH), 7.73 (d, 7 = 8.9 Hz, IH), m/e 355 yl)carbamoyl]phenyl } - 7.64 (d, 7 = 8.9 Hz, IH), 7.44 (d, 7 = 5.1 Hz, IH), 7.35 (M+H)+ l,3-dihydro-2H- (s, IH), 4.94 (t, 7 = 5.9 Hz, IH), 4.82 (d, 7 = 4.3 Hz, pyrrolo[3,4-c]pyridine- IH), 3.49 (d, 7 = 6.0 Hz, 2H), 1.31 (s, 6H)
2-carboxamide
632 N-(4-{ [(2R)-2- ¾ NMR (300 MHz, DMSO- ) δ 8.63 (d, 7 = 9.3 Hz, (ESI(+)) hydroxypropyl] carbarn 2H), 8.50 (d, 7 = 5.0 Hz, IH), 8.21 (t, 7 = 5.7 Hz, IH), m/e 341 oyl}phenyl)-l,3- 7.79 (d, 7 = 8.8 Hz, 2H), 7.65 (d, 7 = 8.8 Hz, 2H), 7.44 (M+H)+ dihydro-2H- (d, 7 = 5.0 Hz, IH), 4.83 (d, 7 = 4.2 Hz, 4H), 4.72 (d, 7
pyrrolo[3,4-c]pyridine- = 4.7 Hz, IH), 3.77 (dt, 7 = 11.9, 6.1 Hz, IH), 3.24 -
2-carboxamide 3.09 (m, 2H), 3.05 (s, IH), 1.06 (d, 7 = 6.2 Hz, 3H) 633 N-(4-{ [(2S)-2- ¾ NMR (300 MHz, DMSO-<¾) δ 8.63 (d, 7 = 8.5 Hz, (ESI(+)) hydroxypropyl] carbarn 2H), 8.50 (d, 7 = 5.0 Hz, 1H), 8.20 (t, J = 5.7 Hz, 1H), m/e 341 oyl}phenyl)-l,3- 7.79 (d, 7 = 8.8 Hz, 1H), 7.65 (d, 7 = 8.8 Hz, 1H), 7.44 (M+H)+ dihydro-2H- (d, 7 = 5.1 Hz, 1H), 4.83 (d, 7 = 4.3 Hz, 4H), 4.72 (d, 7
pyrrolo[3,4-c]pyridine- = 4.7 Hz, 1H), 3.87 - 3.68 (m, 1H), 3.17 (ddd, 7 =
2-carboxamide 15.1, 9.4, 3.6 Hz, 2H), 1.06 (d, 7 = 6.3 Hz, 3H)
634 N-(4-{ [3-(piperidin-l- ¾ NMR (300 MHz, DMSO-<¾) δ 8.63 (d, 7 = 11.4 (ESI(+)) yl)propyl] carbamoyl }p Hz, 2H), 8.50 (d, 7 = 5.0 Hz, 1H), 8.35 (t, 7 = 5.4 Hz, m/e 408 henyl)- 1,3-dihydro- 1H), 7.76 (d, 7 = 8.8 Hz, 2H), 7.65 (d, 7 = 8.8 Hz, 2H), (M+H)+ 2H-pyrrolo[3,4- 7.44 (d, 7 = 5.0 Hz, 1H), 4.82 (d, 7 = 4.3 Hz, 4H), 2.37 c]pyridine-2- - 2.22 (m, 6H), 1.72 - 1.59 (m, 10H), 1.54 - 1.43 (m, carboxamide 20H), 1.38 (d, 7 = 4.8 Hz, 10H)
635 N-[4-(5,6- ¾ NMR (300 MHz, DMSO-<¾) δ 8.64 (d, 7 = 11.8 (ESI(+)) dihydroimidazo[l ,5- Hz, 2H), 8.51 (d, 7 = 5.0 Hz, 1H), 7.68 (d, 7 = 8.6 Hz, m/e 389 a]pyrazin-7(8H)- 2H), 7.61 (s, 1H), 7.43 (t, 7 = 6.9 Hz, 3H), 4.83 (d, 7 = (M+H)+ ylcarbonyl)phenyl] - 4.3 Hz, 4H), 4.74 (s, 2H), 4.12 (t, 7 = 5.4 Hz, 2H),
l,3-dihydro-2H- 3.84 (s, 2H)
pyrrolo[3,4-c]pyridine-
2-carboxamide
686 N-[4-(morpholin-4- ¾ NMR (500 MHz, DMS0-< Temp=90°C) δ 8.69 (ESI(+)) ylcarbonyl)phenyl] - (s, 1H), 8.55 (d, 7 = 3.7, 2H), 7.72 (d, 7 = 5.6, 1H), m/e 353 l,3-dihydro-2H- 7.48 - 7.39 (m, 2H), 7.21 - 7.11 (m, 2H), 4.76 (d, 7 = (M+H)+ pyrrolo[3,4-c]pyridine- 23.4, 4H), 3.40 (s, 8H)
2-carboxamide
687 N-(4-{ [3-(2- ¾ NMR (500 MHz, DMS0-< Temp=90°C) δ 8.88 (ESI(+)) oxopyrrolidin-1- (s, 1H), 8.76 (d, 7 = 5.7, 2H), 8.29 (t, 7 = 5.7, 1H), m/e 408 yl)propyl] carbamoyl }p 7.91 (d, 7 = 5.7, 1H), 7.78 (m, 2H), 7.65 (m, 2H), 4.98 (M+H)+ henyl)- 1, 3-dihydro- (bs, 2H), 4.94 (bs, 2H), 3.35 (t, 7 = 7.0, 2H), 3.22 (m,
2H-pyrrolo[3,4- 4H), 2.22 (t, 7 = 8.0, 2H), 1.92 (m, 2H), 1.70 (p, 7 =
c]pyridine-2- 7.0, 2H)
carboxamide
723 N-{4-[(2- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 H) (ESI(+)) isopropoxyethyl)carba 8.78 (d, 7=6.10 Hz, 1 H) 8.02 (d, 7=5.80 Hz, 1 H) 7.76 m/e 369 moyl]phenyl } - 1 ,3- - 7.81 (m, 2 H) 7.62 - 7.66 (m, 2 H) 5.01 (d, 7=30.82 (M+H)+ dihydro-2H- Hz, 4 H) 3.54 - 3.63 (m, 1 H) 3.49 (t, 7=6.10 Hz, 2 H) pyrrolo[3,4-c]pyridine- 3.38 (t, 7=6.10 Hz, 2 H) 1.09 (d, 7=6.10 Hz, 6 H)
2-carboxamide
724 N-{4-[methyl(3- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 (ESI(+)) methylbutyl)carbamoy H) 8.79 (d, 7=6.10 Hz, 1 H) 8.04 (d, 7=5.80 Hz, 1 H) m/e 367 l]phenyl } - 1 ,3-dihydro- 7.60 (d, 7=8.54 Hz, 2 H) 7.32 (d, 7=7.63 Hz, 2 H) 4.95 (M+H)+
2H-pyrrolo[3,4- - 5.07 (m, 4 H) 3.44 (s, 2 H) 2.89 - 2.96 (m, 3 H) 1.44 c]pyridine-2- (s, 3 H) 0.83 (d, 7=107.41 Hz, 6 H)
carboxamide
725 N-[4-(azetidin-l- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.84 (s, 1 H) (ESI(+)) ylcarbonyl)phenyl] - 8.74 (d, 7=5.80 Hz, 1 H) 7.94 (d, 7=5.80 Hz, 1 H) 7.60 m/e 323 l,3-dihydro-2H- - 7.64 (m, 2 H) 7.56 - 7.59 (m, 2 H) 4.98 (d, 7=24.72 (M+H)+ pyrrolo[3,4-c]pyridine- Hz, 4 H) 4.34 (s, 2 H) 4.05 (d, 7=6.71 Hz, 2 H) 2.22 - 2-carboxamide 2.33 (m, 2 H)
726 N-[4-(2,6- diazaspiro[3.5]non-2- ylcarbonyl)phenyl] - l,3-dihydro-2H- pyrrolo[3,4-c]pyridine- 2-carboxamide 727 N-[4-(l,7- diazaspiro[4.4]non- 1 - ylcarbonyl)phenyl] - l,3-dihydro-2H- pyrrolo[3,4-c]pyridine- 2-carboxamide
728 N-(4-{ [4-(morpholin- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.90 (s, 1 H) (ESI(+)) 4- 8.80 (d, 7=5.80 Hz, 1 H) 8.05 (d, 7=5.80 Hz, 1 H) 7.80 m/e 458 yl)benzyl]carbamoyl}p - 7.85 (m, 2 H) 7.61 - 7.68 (m, 2 H) 7.27 (d, 7=8.54 (M+H)+ henyl)- 1,3-dihydro- Hz, 2 H) 7.05 (d, 7=8.85 Hz, 2 H) 5.02 (d, 7=33.26
2H-pyrrolo[3,4- Hz, 4 H) 4.40 (s, 2 H) 3.76 - 3.81 (m, 4 H) 3.16 - 3.19 c]pyridine-2- (m, 4 H)
carboxamide
729 N-{4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.90 (s, 1 H) (ESI(+))
[(cyclopropylmethyl)c 8.79 (d, 7=5.80 Hz, 1 H) 8.04 (d, 7=6.10 Hz, 1 H) 7.78 m/e 337 arbamoyl]phenyl } - 1 ,3- - 7.82 (m, 2 H) 7.62 - 7.67 (m, 2 H) 5.02 (d, 7=31.73 (M+H)+ dihydro-2H- Hz, 4 H) 3.14 (d, 7=7.02 Hz, 2 H) 0.99 - 1.08 (m, 1 H) pyrrolo[3,4-c]pyridine- 0.40 - 0.48 (m, 2 H) 0.21 - 0.26 (m, 2 H)
2-carboxamide
730 N-{4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 (ESI(+))
[methyl(propyl)carbam H) 8.79 (d, 7=6.10 Hz, 1 H) 8.04 (d, 7=5.80 Hz, 1 H) m/e 339 oyl]phenyl}-l,3- 7.57 - 7.64 (m, 2 H) 7.25 - 7.38 (m, 2 H) 5.01 (d, (M+H)+ dihydro-2H- 7=32.04 Hz, 4 H) 3.17 - 3.45 (m, 2 H) 2.93 (s, 3 H)
pyrrolo[3,4-c]pyridine- 1.53 (d, 7=7.32 Hz, 2 H) 0.64 - 0.97 (m, 3 H)
2-carboxamide
731 N-[4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.90 (s, 1 H) (ESI(+))
(isobu ty lc arb amo yl)ph 8.79 (d, 7=5.80 Hz, 1 H) 8.04 (d, 7=5.80 Hz, 1 H) 7.77 m/e 339 enyl] - 1 ,3 -dihydro-2H- - 7.81 (m, 2 H) 7.60 - 7.65 (m, 2 H) 5.02 (d, 7=31.73 (M+H)+ pyrrolo[3,4-c]pyridine- Hz, 4 H) 3.08 (d, 7=7.02 Hz, 2 H) 1.79 - 1.89 (m, 1 H)
2-carboxamide 0.89 (d, 7=6.71 Hz, 6 H)
732 N-[4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.84 (s, 1 H) (ESI(+))
(butylcarbamoyl)phen 8.74 (d, 7=5.80 Hz, 1 H) 7.94 (d, 7=5.80 Hz, 1 H) 7.76 m/e 339 yl]-l,3-dihydro-2H- - 7.79 (m, 2 H) 7.61 - 7.65 (m, 2 H) 4.98 (d, 7=24.41 (M+H)+ pyrrolo[3,4-c]pyridine- Hz, 4 H) 3.25 (t, 7=7.02 Hz, 2 H) 1.46 - 1.55 (m, 2 H)
2-carboxamide 1.28 - 1.38 (m, 2 H) 0.90 (t, 7=7.32 Hz, 3 H)
733 N-{4-[(2- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.88 (s, 1 H) (ESI(+)) methoxyethyl)carbamo 8.78 (d, 7=5.80 Hz, 1 H) 8.02 (d, 7=5.80 Hz, 1 H) 7.77 m/e 341 yl]phenyl}-l,3- - 7.81 (m, 2 H) 7.60 - 7.65 (m, 2 H) 5.01 (d, 7=29.90 (M+H)+ dihydro-2H- Hz, 4 H) 3.40 - 3.50 (m, 4 H) 3.27 (s, 3 H)
pyrrolo[3,4-c]pyridine-
2-carboxamide
734 N-[4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 (ESI(+))
(cyclopentylcarbamoyl H) 8.79 (d, 7=5.80 Hz, 1 H) 8.03 (d, 7=6.10 Hz, 1 H) m/e 351 )phenyl] - 1 , 3 -dihydro - 7.77 - 7.81 (m, 2 H) 7.60 - 7.65 (m, 2 H) 5.01 (d, (M+H)+ 2H-pyrrolo[3,4- 7=31.43 Hz, 4 H) 4.14 - 4.25 (m, 1 H) 1.82 - 1.99 (m, c]pyridine-2- 2 H) 1.64 - 1.78 (m, 2 H) 1.47 - 1.58 (m, 4 H)
carboxamide
735 N-{4-[(3R)- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.90 (s, 1 H) (ESI(+)) tetrahydrofuran-3- 8.80 (d, 7=6.10 Hz, 1 H) 8.05 (d, 7=6.10 Hz, 1 H) 7.79 m/e 353 ylcarbamoyl]phenyl}- - 7.83 (m, 2 H) 7.61 - 7.67 (m, 2 H) 5.02 (d, 7=32.65 (M+H)+ l,3-dihydro-2H- Hz, 4 H) 4.39 - 4.50 (m, 1 H) 3.85 - 3.90 (m, 2 H) 3.70 pyrrolo[3,4-c]pyridine- - 3.76 (m, 1 H) 3.58 (dd, 7=8.85, 4.27 Hz, 1 H) 2.11 -
2-carboxamide 2.23 (m, 1 H) 1.89 - 1.97 (m, 1 H) 736 N-{4-[(2- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.90 (s, 1 H) (ESI(+)) methoxyethyl) (methyl) 8.79 (d, 7=6.10 Hz, 1 H) 8.04 (d, 7=5.80 Hz, 1 H) 7.60 m/e 355 carbamoyl]phenyl } - (d, 7=8.54 Hz, 2 H) 7.34 (d, 7=8.54 Hz, 2 H) 5.01 (d, (M+H)+ l,3-dihydro-2H- 7=31.73 Hz, 4 H) 3.51 (d, 7=66.52 Hz, 4 H) 3.15 - pyrrolo[3,4-c]pyridine- 3.34 (m, 3 H) 2.94 - 3.02 (m, 3 H)
2-carboxamide
737 N-{4-[(l- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 H) (ESI(+)) methoxypropan-2- 8.79 (d, 7=5.49 Hz, 1 H) 8.03 (d, 7=6.10 Hz, 1 H) 7.77 m/e 355 yl)carbamoyl]phenyl } - - 7.81 (m, 2 H) 7.61 - 7.65 (m, 2 H) 5.02 (d, 7=31.12 (M+H)+ l,3-dihydro-2H- Hz, 4 H) 4.15 - 4.23 (m, 1 H) 3.42 (dd, 7=9.61, 6.56
pyrrolo[3,4-c]pyridine- Hz, 1 H) 3.30 (dd, 7=9.61, 5.95 Hz, 1 H) 3.27 (s, 3 H)
2-carboxamide 1.14 (d, 7=6.71 Hz, 3 H)
738 N-{4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.88 (s, 1 H) (ESI(+))
[(cyclopentylmethyl)ca 8.78 (d, 7=5.80 Hz, 1 H) 8.01 (d, 7=5.80 Hz, 1 H) 7.74 m/e 365 rbamoyl]phenyl } - 1 ,3- - 7.80 (m, 2 H) 7.60 - 7.66 (m, 2 H) 5.01 (d, 7=29.29 (M+H)+ dihydro-2H- Hz, 4 H) 3.18 (d, 7=7.32 Hz, 2 H) 2.08 - 2.21 (m, 1 H) pyrrolo[3,4-c]pyridine- 1.45 - 1.72 (m, 6 H) 1.21 - 1.29 (m, 2 H)
2-carboxamide
739 N-{4-[(2- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.86 (s, 1 H) (ESI(+)) thieny lmethyl) carb amo 8.76 (d, 7=5.80 Hz, 1 H) 7.98 (d, 7=5.80 Hz, 1 H) 7.79 m/e 379 yl]phenyl}-l,3- - 7.85 (m, 2 H) 7.63 - 7.68 (m, 2 H) 7.37 (dd, 7=5.19, (M+H)+ dihydro-2H- 1.22 Hz, 1 H) 7.03 (dd, 7=3.36, 1.22 Hz, 1 H) 6.97
pyrrolo[3,4-c]pyridine- (dd, 7=5.19, 3.36 Hz, 1 H) 5.00 (d, 7=27.16 Hz, 4 H)
2-carboxamide 4.62 (s, 2 H)
740 N-{4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 H) (ESI(+))
[methyl(tetrahydrofura 8.78 (d, 7=5.80 Hz, 1 H) 8.02 (d, 7=5.80 Hz, 1 H) 7.60 m/e 381 n-2- (d, 7=8.54 Hz, 2 H) 7.34 (d, 7=4.58 Hz, 2 H) 5.01 (d, (M+H)+ ylmethyl)carbamoyl]p 7=30.21 Hz, 4 H) 3.93 - 4.23 (m, 2 H) 3.17 - 3.72 (m, henyl } - 1 ,3-dihydro- 3 H) 3.00 (s, 3 H) 1.18 - 2.07 (m, 4 H)
2H-pyrrolo[3,4- c]pyridine-2- carboxamide
741 N-{4-[(3- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 H) (ESI(+)) isopropoxypropyl)carb 8.79 (d, 7=6.10 Hz, 1 H) 8.03 (d, 7=5.80 Hz, 1 H) 7.75 m/e 383 amoyl] pheny 1 } - 1 , 3 - - 7.79 (m, 2 H) 7.61 - 7.67 (m, 2 H) 5.01 (d, 7=31.43 (M+H)+ dihydro-2H- Hz, 4 H) 3.50 - 3.57 (m, 1 H) 3.42 (t, 7=6.26 Hz, 2 H) pyrrolo[3,4-c]pyridine- 3.31 (t, 7=7.02 Hz, 2 H) 1.69 - 1.78 (m, 2 H) 1.09 (d,
2-carboxamide 7=6.10 Hz, 6 H)
742 N-{4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.89 (s, 1 H) (ESI(+))
[benzyl(methyl)carba 8.78 (d, 7=5.80 Hz, 1 H) 8.03 (d, 7=5.80 Hz, 1 H) 7.61 m/e 387 moyl]phenyl } - 1 ,3- (s, 2 H) 7.12 - 7.47 (m, 7 H) 5.00 (d, 7=31.12 Hz, 4 H) (M+H)+ dihydro-2H- 4.49 - 4.74 (m, 2 H) 2.89 (s, 3 H)
pyrrolo[3,4-c]pyridine- 2-carboxamide
743 N-{4-[(3- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.84 (s, 1 (ESI(+)) aminobenzyl)carbamo H) 8.73 (d, 7=5.80 Hz, 1 H) 7.92 (d, 7=5.80 Hz, 1 H) m/e 386 yl]phenyl}-l,3- 7.83 - 7.86 (m, 2 H) 7.64 - 7.68 (m, 2 H) 7.43 (t, (M+H)+ dihydro-2H- 7=7.78 Hz, 1 H) 7.30 (d, 7=7.93 Hz, 1 H) 7.21 (s, 1 H) pyrrolo[3,4-c]pyridine- 7.13 - 7.16 (m, 1 H) 4.98 (d, 7=23.19 Hz, 4 H) 4.49 (s,
2-carboxamide 2 H) 744 N-{4-[(6- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.88 (s, 1 H) (ESI(+)) methoxypyridin-3- 8.77 (d, 7=5.80 Hz, 1 H) 8.48 (d, 7=2.44 Hz, 1 H) 7.98 m/e 390 yl)carbamoyl]phenyl } - - 8.07 (m, 2 H) 7.89 - 7.95 (m, 2 H) 7.69 - 7.74 (m, 2 (M+H)+ l,3-dihydro-2H- H) 6.87 (d, 7=8.85 Hz, 1 H) 5.02 (d, 7=29.29 Hz, 4 H) pyrrolo[3,4-c]pyridine- 3.83 - 3.88 (m, 3 H)
2-carboxamide
745 N-{4-[(3- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.87 (s, 1 H) (ESI(+)) isobutoxypropyl)carba 8.76 (d, 7=5.80 Hz, 1 H) 7.99 (d, 7=5.80 Hz, 1 H) 7.74 m/e 397 moyl]phenyl } - 1 ,3- - 7.80 (m, 2 H) 7.61 - 7.66 (m, 2 H) 5.00 (d, 7=28.07 (M+H)+ dihydro-2H- Hz, 4 H) 3.43 (t, 7=6.26 Hz, 2 H) 3.31 (t, 7=7.02 Hz, 2 pyrrolo[3,4-c]pyridine- H) 3.15 (d, 7=6.71 Hz, 2 H) 1.71 - 1.81 (m, 3 H) 0.86
2-carboxamide (d, 7=6.71 Hz, 6 H)
746 N-{4-[bis(2- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.88 (s, 1 H) (ESI(+)) methoxyethyl)carbamo 8.78 (d, 7=5.80 Hz, 1 H) 8.02 (d, 7=6.10 Hz, 1 H) 7.57 m/e 399 yl]phenyl}-l,3- - 7.61 (m, 2 H) 7.29 - 7.33 (m, 2 H) 5.00 (d, 7=30.82 (M+H)+ dihydro-2H- Hz, 4 H) 3.34 - 3.58 (m, 8 H) 3.12 - 3.32 (m, 6 H)
pyrrolo[3,4-c]pyridine-
2-carboxamide
747 N-{4-[(4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.84 (s, 1 H) (ESI(+)) methoxybenzyl)carba 8.74 (d, 7=5.80 Hz, 1 H) 7.93 (d, 7=5.80 Hz, 1 H) 7.79 m/e 403 moyl]phenyl } - 1 ,3- - 7.83 (m, 2 H) 7.62 - 7.66 (m, 2 H) 7.23 - 7.30 (m, 2 (M+H)+ dihydro-2H- H) 6.86 - 6.93 (m, 2 H) 4.98 (d, 7=24.11 Hz, 4 H) 4.40 pyrrolo[3,4-c]pyridine- (s, 2 H) 3.73 (s, 3 H)
2-carboxamide
748 N-{4-[(3- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.87 (s, 1 H) (ESI(+)) methoxybenzyl)carba 8.77 (d, 7=5.80 Hz, 1 H) 8.00 (d, 7=6.10 Hz, 1 H) 7.81 m/e 403 moyl]phenyl } - 1 ,3- - 7.86 (m, 2 H) 7.63 - 7.68 (m, 2 H) 7.26 (t, 7=7.93 Hz, (M+H)+ dihydro-2H- 1 H) 6.80 - 6.92 (m, 3 H) 5.01 (d, 7=28.99 Hz, 4 H)
pyrrolo[3,4-c]pyridine- 4.44 (s, 2 H) 3.74 (s, 3 H)
2-carboxamide
749 N-(4-{ [4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.88 (s, 1 H) (ESI(+))
(trifluoromethyl)piperi 8.78 (d, 7=6.10 Hz, 1 H) 8.02 (d, 7=6.10 Hz, 1 H) 7.59 m/e 419 din-1- - 7.65 (m, 2 H) 7.32 - 7.38 (m, 2 H) 5.01 (d, 7=30.51 (M+H)+ yl] c arbonyl } phenyl) - Hz, 4 H) 4.55 (d, 7=47.91 Hz, 2 H) 2.75 - 3.24 (m, 2
l,3-dihydro-2H- H) 2.59 - 2.68 (m, 1 H) 1.87 (s, 2 H) 1.34 - 1.49 (m, 2 pyrrolo[3,4-c]pyridine- H)
2-carboxamide
750 N-(4-{ [4-(pyrazin-2- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.90 (s, 1 H) (ESI(+)) yl)piperazin-l- 8.79 (d, 7=5.80 Hz, 1 H) 8.32 (d, 7=1.22 Hz, 1 H) 8.13 m/e 430 yl] c arbonyl } phenyl) - (dd, 7=2.59, 1.37 Hz, 1 H) 8.05 (d, 7=5.80 Hz, 1 H) (M+H)+ l,3-dihydro-2H- 7.88 (d, 7=2.75 Hz, 1 H) 7.61 - 7.68 (m, 2 H) 7.38 - pyrrolo[3,4-c]pyridine- 7.45 (m, 2 H) 5.02 (d, 7=32.34 Hz, 4 H) 3.44 - 3.76
2-carboxamide (m, 8 H)
751 N-{4-[(4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.88 (s, 1 H) (ESI(+)) cyclohexylpiperazin- 1 - 8.78 (d, 7=6.10 Hz, 1 H) 8.01 (d, 7=6.10 Hz, 1 H) 7.57 m/e 434 yl)carbonyl]phenyl } - - 7.69 (m, 2 H) 7.36 - 7.49 (m, 2 H) 5.01 (d, 7=29.29 (M+H)+ l,3-dihydro-2H- Hz, 4 H) 3.96 (s, 1 H) 3.23 - 3.67 (m, 4 H) 2.98 - 3.27 pyrrolo[3,4-c]pyridine- (m, 4 H) 1.04 - 2.15 (m, 10 H)
2-carboxamide
752 N-(4-{ [2-(3,4- ¾ NMR (500 MHz, DMSO-D20) δ ppm 8.88 (s, 1 H) (ESI(+)) dimethoxyphenyl)ethyl 8.77 (d, 7=5.80 Hz, 1 H) 8.01 (d, 7=6.10 Hz, 1 H) 7.73 m/e 447 ]carbamoyl jphenyl)- - 7.80 (m, 2 H) 7.58 - 7.68 (m, 2 H) 6.84 - 6.89 (m, 2 (M+H)+ l,3-dihydro-2H- H) 6.77 (dd, 7=8.09, 1.98 Hz, 1 H) 5.01 (d, 7=29.90
pyrrolo[3,4-c]pyridine- Hz, 4 H) 3.96 (s, 1 H) 3.70 - 3.73 (m, 6 H) 3.46 (t, 2-carboxamide 7=7.32 Hz, 2 H) 2.78 (t, 7=7.32 Hz, 2 H)
770 N-(4-{ [3- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ ppm (ESI(+))
(dimethylamino)propyl 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.70 - 7.78 (m, 2 m/e 368 ]carbamoyl jphenyl)- H) 7.57 - 7.65 (m, 2 H) 7.41 (d, 7=4.88 Hz, 1 H) 4.80 - (M+H)+ l,3-dihydro-2H- 4.87 (m, 4 H) 3.30 - 3.34 (m, 2 H) 2.28 - 2.40 (m, 2 H) pyrrolo[3,4-c]pyridine- 2.17 - 2.21 (m, 6 H) 1.61 - 1.75 (m, 2 H)
2-carboxamide
771 N-(4-{ [3-(morpholin- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ ppm (ESI(+)) 4- 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.69 - 7.79 (m, 2 m/e 410 yl)propyl] carbamoyl }p H) 7.57 - 7.64 (m, 2 H) 7.41 (d, 7=5.19 Hz, 1 H) 4.80 - (M+H)+ henyl)- 1,3-dihydro- 4.87 (m, 4 H) 3.54 - 3.62 (m, 4 H) 3.31 - 3.34 (m, 2 H)
2H-pyrrolo[3,4- 2.34 - 2.42 (m, 6 H) 1.65 - 1.76 (m, 2 H)
c]pyridine-2- carboxamide
772 N-(4-{ [4-(2- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ ppm (ESI(+)) aminoethyl)-lH- 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.71 - 7.76 (m, 2 m/e 377 imidazol-1- H) 7.57 - 7.66 (m, 2 H) 7.52 (s, 1 H) 7.41 (d, 7=5.19 (M+H)+ yl] c arbonyl } phenyl) - Hz, 1 H) 6.82 (s, 1 H) 4.78 - 4.86 (m, 4 H) 3.51 (t,
l,3-dihydro-2H- 7=7.32 Hz, 2 H) 2.80 (t, 7=7.02 Hz, 2 H)
pyrrolo[3,4-c]pyridine-
2-carboxamide
773 N-[4-({4-[2-(2- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ ppm (ESI(+)) hydroxyethoxy) ethyl] p 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.56 - 7.62 (m, 2 m/e 440 iperazin-1- H) 7.41 (d, 7=5.19 Hz, 1 H) 7.27 - 7.33 (m, 2 H) 4.79 - (M+H)+ yl } carbonyl)phenyl] - 4.87 (m, 4 H) 3.40 - 3.60 (m, 10 H) 2.53 - 2.57 (m, 2 l,3-dihydro-2H- H) 2.43 - 2.50 (m, 4 H)
pyrrolo[3,4-c]pyridine-
2-carboxamide
774 N-{4-[(3- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ ppm (ESI(+)) hydroxypropyl)carbam 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.71 - 7.78 (m, 2 m/e 341 oyl]phenyl}-l,3- H) 7.58 - 7.63 (m, 2 H) 7.41 (d, 7=5.19 Hz, 1 H) 4.78 - (M+H)+ dihydro-2H- 4.89 (m, 4 H) 3.51 (t, 7=6.26 Hz, 2 H) 3.34 (t, 7=6.87 pyrrolo[3,4-c]pyridine- Hz, 2 H) 1.65 - 1.79 (m, 2 H)
2-carboxamide
775 N-(4-{ [4- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ ppm (ESI(+))
(dimethylamino)butyl] 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.71 - 7.77 (m, 2 m/e 382 carbamoyl } phenyl) - H) 7.58 - 7.64 (m, 2 H) 7.42 (d, 7=4.88 Hz, 1 H) 4.79 - (M+H)+ l,3-dihydro-2H- 4.88 (m, 4 H) 3.27 (t, 7=6.87 Hz, 2 H) 2.26 - 2.33 (m, pyrrolo[3,4-c]pyridine- 2 H) 2.16 (s, 6 H) 1.41 - 1.61 (m, 4 H)
2-carboxamide
776 N-{4-[(pyridin-4- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ (ESI(+)) ylmethyl)carbamoyl]p ppm 8.59 (s, 1 H) 8.46 - 8.50 (m, 3 H) 7.79 - 7.84 (m, m/e 374 henyl } - 1 ,3-dihydro- 2 H) 7.62 - 7.67 (m, 2 H) 7.42 (d, 7=4.88 Hz, 1 H) (M+H)+
2H-pyrrolo[3,4- 7.31 (d, 7=6.10 Hz, 2 H) 4.84 (d, 7=7.02 Hz, 4 H) 4.49 c]pyridine-2- (s, 2 H)
carboxamide
777 N-{4-[(pyridin-3- ¾ NMR (400 MHz, DMSO-D20 Temp=90°C) δ ppm (ESI(+)) ylmethyl)carbamoyl]p 8.58 (s, 1 H) 8.54 (d, 7=1.83 Hz, 1 H) 8.48 (d, 7=5.19 m/e 374 henyl } - 1 ,3-dihydro- Hz, 1 H) 8.43 (dd, 7=4.88, 1.53 Hz, 1 H) 7.77 - 7.82 (M+H)+
2H-pyrrolo[3,4- (m, 2 H) 7.71 - 7.75 (m, 1 H) 7.60 - 7.66 (m, 2 H) 7.41 c]pyridine-2- (d, 7=5.19 Hz, 1 H) 7.34 (dd, 7=7.93, 5.49 Hz, 1 H)
carboxamide 4.79 - 4.88 (m, 4 H) 4.44 - 4.53 (m, 2 H)
Figure imgf000724_0001
Figure imgf000725_0001
2-carboxamide 4H)
Figure imgf000726_0001
2-carboxamide 1.56- 1.34 (m, 2H) 1059 N-[4-(2,9- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.62 - 8.46 (ESI(+)) diazaspiro[5.5]undec- (m, 2H), 7.85 (dd, J = 43.4, 8.8 Hz, 2H), 7.52 - 7.43 m/e 420 2-ylcarbonyl)phenyl] - (m, 2H), 7 .10 (d, 7 = 4.9 Hz, 1H), 3.90 - 3.70 (m, (M+H)+ l,3-dihydro-2H- 1H), 3.60 - 3.43 (m, 3H), 3.41 - 3.25 (m, 1H), 3.24 - pyrrolo[3,4-c]pyridine- 3.03 (m, 4H), 1.89 - 1.56 (m, 4H), 1.54 - 1.31 (m, 4H)
2-carboxamide
1060 N-[4-(2,8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.56 (dd, 7 = (ESI(+))
diazaspiro[5.5]undec- 9.9, 4.6 Hz, 2H), 8.12 - 7.80 (m, 2H), 7.52 - 7.43 (m, m/e 420 2-ylcarbonyl)phenyl] - 3H), 4.90 - 4.83 (m, 6H), 3.67 - 3.55 (m, 2H), 3.49 - (M+H)+ l,3-dihydro-2H- 3.37 (m, 2H), 3.41 - 3.23 (m, 4H), 1.99 - 1.61 (m,
pyrrolo[3,4-c]pyridine- 4H), 1.47 (d, 7 = 10.4 Hz, 4H)
2-carboxamide
1061 N-[4-(l,8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.60 - 8.44 (ESI(+))
diazaspiro[5.5]undec- (m, 2H), 7.86 (t, 7 = 25.2 Hz, 2H), 7.54 (t, 7 = 6.9 Hz, m/e 420 8 -ylcarbonyl)phenyl] - 2 H), 7.10 (d, 7 = 4.9 Hz, 1H), 4.14 (d, 7 = 13.5 Hz, (M+H)+ l,3-dihydro-2H- 1H), 4.02 (d, 7 = 13.5 Hz, 1H), 3.59 (dd, 7 = 11.5, 6.5 pyrrolo[3,4-c]pyridine- Hz, 1H), 3.48 - 3.33 (m, 1H), 3.36 - 3.13 (m, 2H),
2-carboxamide 2.23 (ddd, 7 = 13.3, 8.9, 4.3 Hz, 1H), 1.96 - 1.82 (m,
2H), 1.83 - 1.65 (m, 4H), 1.69 - 1.44 (m, 4H)
1062 N-[4-(l,8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.50 (dd, 7 = (ESI(+))
diazaspiro[4.6]undec- 43.2, 14.6 Hz, 2H), 7.98 - 7.82 (m, 2H), 7.52 - 7.41 m/e 420 8 -ylcarbonyl)phenyl] - (m, 2H), 7.10 (d, 7 = 4.9 Hz, 1H), 3.95 - 3.75 (m, 1H), (M+H)+ l,3-dihydro-2H- 3.67 (d, 7 = 9.3 Hz, 2H), 3.51 - 3.37 (m, 6H), 2.52 - pyrrolo[3,4-c]pyridine- 2.33 (m, 1H), 2.25 - 2.11 (m, 2H), 2.12 - 1.99 (m,
2-carboxamide 1H), 2.03 - 1.83 (m, 6H), 1.66 (d, 7 = 41.1 Hz, 1H)
1063 N-{4-[(l-oxa-8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.61 - 8.44 (ESI(+))
azaspiro[4.5]dec-2- (m, 2H), 8.18 - 8.03 (m, 2H), 7.98 - 7.81 (m, 2H), m/e 436 ylmethyl)c arb amoyl] p 7.10 (d, 7 = 4.9 Hz, 1H) 4.89 - 4.79 (m, 6H), 4.28 (dt, (M+H)+ henyl } - 1 ,3-dihydro- 7 = 12.4, 6.2 Hz, 1H), 3.80 - 3.64 (m, 2H), 3.51 (s,
2H-pyrrolo[3,4- 1H), 3.45 - 3.25 (m, 4H), 2.12 - 1.89 (m, 2H), 1.87 - c]pyridine-2- 1.48 (m, 4H)
carboxamide
1064 N-[4-(l-oxa-8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.44 (d, 7 = (ESI(+))
azaspiro[4.5]dec-3- 20.6 Hz, 1H), 7.88 (t, 7 = 10.7 Hz, 3H), 7.69 - 7.57 m/e 422 ylcarbamoyl)phenyl] - (m, 3H), 4.22 (d, 7 = 12.3 Hz, 1H), 3.93 (dt, 7 = 11.3, (M+H)+ l,3-dihydro-2H- 8.0 Hz, 2H), 3.83 - 3.64 (m, 3H), 3.59 - 3.46 (m, 3H), pyrrolo[3,4-c]pyridine- 3.45 - 3.31 (m, 1H), 2.71 - 2.46 (m, 1H), 2.12 - 1.80
2-carboxamide (m, 8H)
1065 N-{4-[(2-oxa-9- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.56 - 8.44 (ESI(+))
azaspiro[5.5]undec-3- (m, 2H), 8.26 - 8.00 (m, 3H), 7.87 (dd, 7 = 40.3, 8.7 m/e 450 ylmethyl)c arb amoyl] p Hz, 2H), 3.99 - 3.70 (m, 2H), 3.66 - 3.56 (m, 2H), (M+H)+ henyl } - 1 ,3-dihydro- 3.51 (s, 1H), 3.35 - 3.16 (m, 4H), 3.10 (d, 7 = 11.5 Hz,
2H-pyrrolo[3,4- 1H), 2.09 - 1.82 (m, 2H), 1.83 - 1.68 (m, 1H), 1.61 - c]pyridine-2- 1.36 (m, 4H), 1.33 - 1.05 (m, 1H)
carboxamide
1066 N-[4-(l-oxa-4,8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.62 - 8.46 (ESI(+))
diazaspiro[5.5]undec- (m, 2H), 7.86 (dd, 7 = 52.3, 8.6 Hz, 3H), 7.56 (d, 7 = m/e 422
4-ylcarbonyl)phenyl] - 15.9 Hz, 2H), 4.94 - 4.73 (m, 5H), 3.81 - 3.52 (m, (M+H)+ l,3-dihydro-2H- 6H), 3.37 (d, 7 = 12.4 Hz, 1H), 3.17 - 2.87 (m, 2H), pyrrolo[3,4-c]pyridine- 2.13 - 1.83 (m, 2H), 1.63 - 1.24 (m, 2H)
2-carboxamide
1067 N-[4-(l,8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.59 - 8.45 (ESI(+))
diazaspiro [4.5] dec- 1 - (m, 2H), 7.96 - 7.80 (m, 2H), 7.59 - 7.52 (m, 2H), m/e 406 ylcarbonyl)phenyl] - 7.10 (d, 7 = 4.9 Hz, 1H ), 4.87 (d, 7 = 6.5 Hz, 6H), (M+H)+ l,3-dihydro-2H- 3.54 (dt, 7 = 13.2, 4.8 Hz, 4H), 3.41 (dd, 7 = 9.0, 4.4
pyrrolo[3,4-c]pyridine- Hz, 2H), 3.28 - 3.12 (m, 2H), 2.03 - 1.86 (m, 2H),
2-carboxamide 1.74 - 1.46 (m, 4H)
1068 N-[4-(l,8- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.50 (dd, 7 = (ESI(+))
diazaspiro [4.5] dec- 8 - 44.5, 13.2 Hz, 2H), 7.88 (d, 7 = 8.5 Hz, 2H), 7.50 (d, 7 m/e 406 ylcarbonyl)phenyl] - = 8.6 Hz, 2H), 7 .10 (d, 7 = 4.9 Hz, 1H), 4.14 - 3.91 (M+H)+ l,3-dihydro-2H- (m, 2H), 3.66 - 3.34 (m, 6H), 2.43 (s, 1H), 2.23 - 2.05 pyrrolo[3,4-c]pyridine- (m, 2H), 2.05 - 1.66 (m, 8H)
2-carboxamide
1069 N-[4-(l,7- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.59 - 8.43 (ESI(+))
diazaspiro[3.5]non-7- (m, 2H), 7.90 (d, 7 = 8.5 Hz, 2H), 7.48 (t, 7 = 13.3 Hz, m/e 392 ylcarbonyl)phenyl] - 3H), 4.90 (dd, 7 = 29.4, 12.8 Hz, 4H), 4.01 (d, 7 = 47.2 (M+H)+ l,3-dihydro-2H- Hz, 2H), 3.61 (t, 7 = 5.7 Hz, 2H), 3.51 (s, 2H), 3.37 (t, pyrrolo[3,4-c]pyridine- 7 = 7.4 Hz, 2H), 2.61 (t, 7 = 7.3 Hz, 2H), 2.10 (s, 2H)
2-carboxamide
1070 N-[4-(l,6- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.56 (d, 7 = (ESI(+))
diazaspiro[3.5]non- 1 - 6.6 Hz, 2H), 8.05 - 7.86 (m, 2H), 7.82 - 7.62 (m, 2H), m/e 392 ylcarbonyl)phenyl] - 7.10 (d, 7 = 4.9 Hz, 1H), 4.98 - 4.75 (m, 4H), 4.27 (td, (M+H)+ l,3-dihydro-2H- 7 = 8.9, 6.8 Hz, 1H), 3.96 (ddd, 7 = 25.0, 14.5, 9.4 Hz, pyrrolo[3,4-c]pyridine- 3H), 3.51 (d, 7 = 6.5 Hz, 1H), 3.44 (t, 7 = 9.6 Hz, 1H),
2-carboxamide 3.23 (tdd, 7 = 12.8, 11.1, 4.3 Hz, 2H), 2.58 - 2.45 (m,
1H), 2.39 - 2.19 (m, 1H), 1.97 (ddd, 7 = 11.3, 9.0, 5.2
Hz, 2H), 1.89 - 1.63 (m, 2H)
1071 N-[4-(2,5- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.59 - 8.44 (ESI(+))
diazaspiro[3.5]non-2- (m, 2H), 7.90 (d, 7 = 8.7 Hz, 2H), 7.84 - 7.67 (m, 2H), m/e 392 ylcarbonyl)phenyl] - 7.10 (d, 7 = 4.9 Hz, 1H), 4.89 (dd, 7 = 31.4, 12.8 Hz, (M+H)+ l,3-dihydro-2H- 4H), 4.38 (d, 7 = 9.7 Hz, 2H), 4.29 - 4.03 (m, 2H),
pyrrolo[3,4-c]pyridine- 3.51 (s, 1H), 3.12 - 2.82 (m, 2H), 2.01 - 1.69 (m, 2H),
2-carboxamide 1.62 - 1.22 (m, 4H)
1072 N-[4-(5-oxa-2- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.60 - 8.44 (ESI(+))
azaspiro [3.4] oct-2- (m, 3H), 7.99 - 7.85 (m, 2H), 7.85 - 7.74 (m, 2H), m/e 379 ylcarbonyl)phenyl] - 7.10 (d, 7 = 4.9 Hz, 1H), 4.98 - 4.74 (m, 4H), 4.41 - (M+H)+ l,3-dihydro-2H- 4.24 (m, 3H), 4.19 (dd, 7 = 9.6, 1.2 Hz, 2H), 3.85 - pyrrolo[3,4-c]pyridine- 3.61 (m, 2H), 1.92 (t, 7 = 7.3 Hz, 2H), 1.80 - 1.54 (m,
2-carboxamide 2H)
1073 N-[4-(6-oxa-2- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.58 - 8.43 (ESI(+))
azaspiro [3.5]non-2- (m, 2H), 7.91 (dd, 7 = 21.0, 8.7 Hz, 2H), 7.85 (t, 7 = m/e 393 ylcarbonyl)phenyl] - 7.0 Hz, 2H), 7.11 (d, 7 = 4.9 Hz, 1H), 4.88 (t, 7 = 13.2 (M+H)+ l,3-dihydro-2H- Hz, 4H), 4.04 - 3.91 (m, 2H), 3.91 - 3.76 (m, 2H),
pyrrolo[3,4-c]pyridine- 3.62 - 3.54 (m, 2H), 3.54 - 3.36 (m, 3H), 1.77 - 1.52
2-carboxamide (m, 2H), 1.52 - 1.27 (m, 2H)
1074 N-[4-(hexahydro-5H- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.57 - 8.46 (ESI(+))
furo[2,3-c]pyrrol-5- (m, 2H), 7.98 - 7.76 (m, 2H), 7.69 - 7.57 (m, 2H), m/e 379 ylcarbonyl)phenyl] - 7.10 (s, 1H), 4.86 (dd, 7 = 17.1, 10.2 Hz, 4H), 4.39 (t, (M+H)+ l,3-dihydro-2H- 7 = 5.6 Hz, 1H), 3.98 - 3.81 (m, 2H), 3.74 - 3.54 (m, pyrrolo[3,4-c]pyridine- 4H), 3.56 - 3.41 (m, 1H), 2.78 - 2.51 (m, 1H), 2.07 -
2-carboxamide 1.72 (m, 1H), 1.73 - 1.36 (m, 1H)
1075 N-[4-(tetrahydro-lH- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.59 - 8.46 (ESI(+))
furo [3,4 -c]pyrrol- (m, 2H), 7.90 (d, 7 = 8.6 Hz, 2H), 7.68 - 7.58 (m, 2H), m/e 379 5(3H)- 7.10 (d, 7 = 5.0 Hz, 1H), 4.87 (dd, 7 = 16.8, 9.9 Hz, (M+H)+ ylcarbonyl)phenyl] - 4H), 3.86 - 3.64 (m, 4H), 3.64 - 3.40 (m, 5H), 2.86 - l,3-dihydro-2H- 2.58 (m, 2H)
pyrrolo[3,4-c]pyridine- 2-carboxamide 1076 N-[4- ¾ NMR (400 MHz, Pyridine-^) δ ppm 8.62 - 8.45 (ESI(+))
(hexahydrofuro [3,4- (m, 2H), 8.01 - 7.80 (m, 2H), 7.57 - 7.52 (m, 2H), m/e 393 c]pyridin-5(3H)- 7.10 (d, 7 = 5.1 Hz, 1H), 4.91 - 4.78 (m, 4H), 3.83 - (M+H)+ ylcarbonyl)phenyl] - 3.69 (m, 2H), 3.74 - 3.55 (m, 6H), 3.45 - 3.26 (m,
l,3-dihydro-2H- 1H), 2.37 - 2.17 (m, 2H), 1.72 - 1.35 (m, 2H)
pyrrolo[3,4-c]pyridine-
2-carboxamide
1120 N-(4-{ [3-(5-methyl- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.47 (ESI(+)) lH-pyrazol-1- (d, 7 = 4.9 Hz, 1H), 7.80 (d, 7 = 7.7 Hz, 1H), 7.78 - m/e 405 yl)propyl] carbamoyl }p 7.70 (m, 2H), 7.70 - 7.54 (m, 2H), 7.42 - 7.09 (m, (M+H)+ henyl) - 5 , 7 -dihy dro - 2H), 6.01 (d, 7 = 0.8 Hz, 1H), 4.81 (d, 7 = 11.5 Hz,
6H-pyrrolo[3,4- 4H), 4.08 (t, 7 = 7.0 Hz, 2H), 3.32 - 3.27 (m, 2H),
b]pyridine-6- 2.25 (s, 3H), 2.12 - 1.94 (m, 2H)
carboxamide
1121 N-(4-{ [2-(4-chloro- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.52 - (ESI(+)) lH-pyrazol-1- 8.38 (m, 1H), 7.87 - 7.76 (m, 2H), 7.73 - 7.66 (m, m/e 411 yl)ethyl] carbamoyl } ph 2H), 7.66 - 7.55 (m, 2H), 7.54 - 7.39 (m, 1H), 7.38 - (M+H)+ enyl) -5,7 -dihydro-6H- 7.22 (m, 1H), 4.95 - 4.64 (m, 4H), 4.28 (dd, 7 = 8.0, pyrrolo[3,4-b]pyridine- 4.5 Hz, 2H), 3.79 - 3.50 (m, 2H)
6-carboxamide
1122 N-(4-{ [l-(3,5- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.47 (t, (ESI(+)) dimethyl- 1 H-pyrazol- 7 = 9.6 Hz, 1H), 7.91 - 7.78 (m, 1H), 7.79 - 7.68 (m, m/e 419 l-yl)propan-2- 2H), 7.68 - 7.57 (m, 2H), 7.38 - 7.31 (m, 1H), 4.82 (d, (M+H)+ yl]carbamoyl jphenyl)- 7 = 8.8 Hz, 4H), 4.37 (h, 7 = 6.7 Hz, 1H), 4.24 - 3.93
5,7-dihydro-6H- (m, 2H), 2.89 - 2.68 (m, 1H), 2.63 - 2.42 (m, 2H),
pyrrolo[3,4-b]pyridine- 2.13 (s, 3H), 1.96 (s, 1H), 1.27 - 1.02 (m, 3H)
6-carboxamide
1123 N-(4-{ [2-methyl-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.47 (ESI(+))
(morpholin-4- (d, J = 4.8 Hz, 1H), 7.81 (dd, 7 = 10.0, 8.1 Hz, 3H), m/e 438 yl)butyl]carbamoyl}ph 7.75 - 7.60 (m, 2H), 7.46 - 7.25 (m, 1H), 4.81 (d, J = (M+H)+ enyl) -5,7 -dihydro-6H- 12.8 Hz, 4H), 3.92 (s, 4H), 3.40 (s, 3H), 2.85 (dd, 7 = pyrrolo[3,4-b]pyridine- 84.9, 29.4 Hz, 2H), 2.57 - 2.38 (m, 3H), 1.92 (d, 7 =
6-carboxamide 35.3 Hz, 1H), 1.87 - 1.66 (m, 2H), 1.02 (t, 7 = 7.4 Hz,
3H)
1124 N-{4-[(4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.55 - (ESI(+)) methoxybenzyl)carba 8.39 (m, 1H), 7.98 - 7.71 (m, 3H), 7.67 - 7.52 (m, m/e 403 moyl] phenyl } -5 ,7 - 2H), 7.36 - 7.29 (m, 1H), 7.29 - 7.17 (m, 2H), 6.98 - (M+H)+ dihy dro- 6H - 6.73 (m, 2H), 4.90 - 4.60 (m, 4H), 4.38 (d, 7 = 17.5
pyrrolo[3,4-b]pyridine- Hz, 2H), 3.74 (d, 7 = 3.2 Hz, 3H)
6-carboxamide
1125 N-(4-{ [3-(morpholin- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.57 - (ESI(+))
4- 8.35 (m, 1H), 7.89 - 7.72 (m, 3H), 7.72 - 7.54 (m, m/e 410 yl)propyl] carbamoyl }p 2H), 7.33 (dd, 7 = 7.7, 5.0 Hz, 1H), 4.81 (d, 7 = 11.8 (M+H)+ henyl) - 5 , 7 -dihy dro - Hz, 4H), 3.86 (s, 4H), 3.47 - 3.34 (m, 2H), 3.24 - 3.04
6H-pyrrolo[3,4- (m, 2H), 2.12 - 1.78 (m, 2H)
b]pyridine-6- carboxamide
1126 N-[4-({4-[2-(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.46 (ESI(+)) hydroxyethoxy) ethyl] p (dd, 7 = 12.7, 2.9 Hz, 1H), 7.80 (d, 7 = 7.7 Hz, 1H), m/e 440 iperazin-1- 7.73 - 7.55 (m, 2H), 7.49 - 7.35 (m, 2H), 7.35 - 7.25 (M+H)+ yl } carbonyl)phenyl] - (m, 1H), 4.81 (d, 7 = 11.4 Hz, 4H), 3.90 - 3.71 (m,
5,7-dihydro-6H- 6H), 3.66 - 3.48 (m, 5H), 3.37 (d, 7 = 5.2 Hz, 5H),
pyrrolo[3,4-b]pyridine- 2.88 (d, 7 = 53.2 Hz, 4H), 1.96 (s, 2H)
6-carboxamide 1127 N-{4-[(2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.46 (ESI(+)) carbamoylbenzyl)carb (d, J = 4.3 Hz, 1H), 7.84 - 7.73 (m, 3H), 7.73 - 7.59 m/e 416 amoyl]phenyl} -5,7- (m, 2H), 7.48 (d, J = 7.4 Hz, 1H), 7.44 - 7.37 (m, 2H), (M+H)+ dihydro-6H- 7.37 - 7.20 (m, 2H), 4.81 (d, J = 12.6 Hz, 4H), 4.63 (s, pyrrolo[3,4-b]pyridine- 2H)
6-carboxamide
1128 ST-{4-[bis(2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.65 - (ESI(+)) methoxyethyl)carbamoy 8.37 (m, 1H), 7.78 (dd, J = 40.2, 6.3 Hz, 1H), 7.68 - m/e 399
] phenyl } -5 , 7 -dihydro - 7.53 (m, 2H), 7.42 - 7.31 (m, 1H), 7.32 - 7.20 (m, (M+H)+
5H-pyrrolo[3,4- 2H), 4.85 (t, J = 26.3 Hz, 4H), 3.67 - 3.41 (m, 9H),
?]pyridine-6- 3.28 (t, J = 8.4 Hz, 6H), 3.06 - 2.71 (m, 2H), 2.01 (d, J
:arboxamide = 38.9 Hz, 1H)
1129 N-{4-[(l-amino-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.59 - (ESI(+)) oxohexan-2- 8.22 (m, 1H), 7.89 - 7.75 (m, 3H), 7.70 - 7.54 (m, m/e 394 yl)carbamoyl]phenyl } - 2H), 7.37 (dd, J = 7.7, 5.0 Hz, 1H), 4.83 (d, J = 8.7 (M+H)+
5,7-dihydro-6H- Hz, 4H), 4.41 (dd, J = 8.6, 5.5 Hz, 1H), 3.11 - 2.72
pyrrolo[3,4-b]pyridine- (m, 1H), 2.53 - 2.31 (m, 1H), 1.90 - 1.56 (m, 2H),
6-carboxamide 1.48 - 1.22 (m, 4H), 1.11 - 0.77 (m, 3H)
1130 N-(4-{ [2-(3,4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.55 - (ESI(+)) dimethoxyphenyl)ethyl 8.34 (m, 1H), 7.87 - 7.75 (m, 1H), 7.76 - 7.67 (m, m/e 447
]carbamoyl jphenyl)- 2H), 7.67 - 7.52 (m, 2H), 7.45 - 7.26 (m, 1H), 6.94 - (M+H)+
5,7-dihydro-6H- 6.79 (m, 2H), 6.77 (dd, J = 8.1, 2.0 Hz, 1H), 4.90 - pyrrolo[3,4-b]pyridine- 4.61 (m, 4H), 3.73 (d, J = 2.9 Hz, 6H), 3.63 - 3.35 (m,
6-carboxamide 2H), 2.87 - 2.66 (m, 2H)
1131 N-(4-{ [4-(pyrazin-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.31 - (ESI(+)) yl)piperazin-l- 8.22 (m, 1H), 8.12 - 8.04 (m, 1H), 7.90 - 7.59 (m, m/e 430 yl] c arbonyl } phenyl) - 4H), 7.43 - 7.30 (m, 3H), 4.87 - 4.75 (m, 4H), 3.69 - (M+H)+
5,7-dihydro-6H- 3.60 (m, 8H)
pyrrolo[3,4-b]pyridine-
6-carboxamide
1132 Nalpha-{4-[(5,7- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.57 - (ESI(+)) dihydro-6H- 8.27 (m, 1H), 7.83 - 7.74 (m, 1H), 7.74 - 7.64 (m, m/e 430 pyrrolo[3,4-b]pyridin- 2H), 7.64 - 7.54 (m, 2H), 7.39 - 7.20 (m, 5H), 7.20 - (M+H)+ 6- 7.09 (m, 1H), 4.88 - 4.73 (m, 4H), 4.73 - 4.58 (m,
ylcarbonyl)amino]benz 1H), 3.22 - 3.11 (m, 1H), 3.11 - 2.92 (m, 1H)
oyl}-L- phenylalaninamide
1133 N-(4-{ [(2R)-l -amino- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.61 - (ESI(+))
4-methyl- 1 -oxopentan- 8.35 (m, 1H), 7.96 - 7.73 (m, 3H), 7.71 - 7.53 (m, m/e 396 2- 2H), 7.47 - 7.28 (m, 1H), 4.94 - 4.67 (m, 4H), 4.61 - (M+H)+ yl]carbamoyl jphenyl)- 4.34 (m, 1H), 3.08 - 2.71 (m, 1H), 1.93 - 1.49 (m,
5,7-dihydro-6H- 2H), 1.00 - 0.70 (m, 6H)
pyrrolo[3,4-b]pyridine- 6-carboxamide
1134 N-{4-[(4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.48 (ESI(+)) cyclohexylpiperazin- 1 - (d, J = 4.6 Hz, 1H), 7.91 - 7.76 (m, 1H), 7.75 - 7.57 m/e 434 yl)carbonyl]phenyl } - (m, 2H), 7.50 - 7.27 (m, 3H), 4.86 (t, J = 26.6 Hz, (M+H)+ 5,7-dihydro-6H- 4H), 3.80 (s, 3H), 3.28 - 3.13 (m, 2H), 3.05 - 2.73 (m, pyrrolo[3,4-b]pyridine- 3H), 2.70 - 2.43 (m, 1H), 2.09 (d, J = 11.0 Hz, 2H),
6-carboxamide 1.84 (t, J = 13.9 Hz, 2H), 1.64 (d, J = 12.9 Hz, 1H),
1.48 - 1.22 (m, 4H), 1.22 - 1.04 (m, 1H)
1135 N-{4-[(3-tert- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.48 (ESI(+)) butoxypropyl)carbamo (d, J = 4.4 Hz, 1H), 7.80 (t, J = 17.2 Hz, 1H), 7.76 - m/e 394 yl]phenyl}-5,7- 7.65 (m, 2H), 7.68 - 7.52 (m, 2H), 7.36 (dd, J = 7.7, (M+H)+
Figure imgf000731_0001
pyrrolo[3,4-b]pyridine- 6-carboxamide
1195 N-{4-[(3-methoxy-2,2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.47 (t, (ESI(+)) dimethylpropyl)carba J = 12.9 Hz, 1H), 7.85 (d, 7 = 7.7 Hz, 1H), 7.79 - 7.69 m/e 388 moyl] phenyl } -5 ,7 - (m, 2H), 7.69 - 7.57 (m, 2H), 7.38 (dd, 7 = 7.7, 5.0 (M+H)+ dihydro-6H- Hz, 1H), 4.83 (d, 7 = 8.0 Hz, 4H), 3.30 (s, 3H), 3.21 (s, pyrrolo[3,4-b]pyridine- 2H), 3.15 (s, 2H), 0.90 (s, 6H)
6-carboxamide
1196 N-{4-[(3,3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.48 (ESI(+)) dimethylbutyl)carbam (d, 7 = 4.4 Hz, 1H), 7.82 (d, 7 = 7.7 Hz, 1H), 7.78 - m/e 367 oyl]phenyl}-5,7- 7.69 (m, 2H), 7.69 - 7.57 (m, 2H), 7.35 (dd, 7 = 7.7, (M+H)+ dihydro-6H- 5.0 Hz, 1H), 4.82 (d, 7 = 10.1 Hz, 4H), 3.31 (d, 7 = 4.0 pyrrolo[3,4-b]pyridine- Hz, 1H), 3.28 (s, 1H), 1.60 - 1.24 (m, 2H), 0.94 (s,
6-carboxamide 9H)
1197 N-(4-{ [l-(furan-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.63 - (ESI(+)) yl)propan-2- 8.39 (m, 1H), 7.89 - 7.79 (m, 1H), 7.79 - 7.67 (m, m/e 391 yl]carbamoyl jphenyl)- 2H), 7.67 - 7.51 (m, 2H), 7.51 - 7.27 (m, 1H), 6.32 (M+H)+
5,7-dihydro-6H- (dd, 7 = 3.1, 1.9 Hz, 1H), 6.13 (dd, 7 = 3.2, 0.7 Hz,
pyrrolo[3,4-b]pyridine- 1H), 4.86 (t, 7 = 25.1 Hz, 4H), 4.28 (h, 7 = 6.7 Hz,
6-carboxamide 1H), 3.06 - 2.73 (m, 4H), 1.96 (s, 1H), 1.19 (1, 7 = 5.9
Hz, 3H)
1198 N-(4-{ [(3-methyl-l,2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.59 - (ESI(+)) oxazol-5- 8.37 (m, 1H), 7.87 - 7.70 (m, 3H), 7.71 - 7.52 (m, m/e 378 yl)methyl] carbamoyl } 2H), 7.42 - 7.20 (m, 1H), 6.24 - 6.02 (m, 1H), 4.93 - (M+H)+ phenyl) -5,7 -dihydro- 4.69 (m, 4H), 4.64 - 4.44 (m, 2H), 2.20 (s, 3H)
6H-pyrrolo[3,4- b]pyridine-6- carboxamide
1199 N-(4-{ [(2R)-l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.49 (t, (ESI(+)) cyanobutan-2- 7 = 7.9 Hz, 1H), 7.96 - 7.83 (m, 1H), 7.83 - 7.73 (m, m/e 364 yl]carbamoyl jphenyl)- 2H), 7.71 - 7.54 (m, 2H), 7.39 (dd, 7 = 7.7, 5.1 Hz, (M+H)+
5,7-dihydro-6H- 1H), 4.83 (d, 7 = 7.3 Hz, 4H), 4.27 - 3.97 (m, 1H),
pyrrolo[3,4-b]pyridine- 2.89 - 2.62 (m, 3H), 1.97 (s, 1H), 1.68 (p, 7 = 7.3 Hz,
6-carboxamide 2H), 0.93 (t, 7 = 7.4 Hz, 3H)
1200 N-{4-[methyl(3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.48 (ESI(+)) methylbutyl)carbamoy (dd, 7 = 5.4, 4.9 Hz, 1H), 7.84 (dd, 7 = 7.7, 0.7 Hz, m/e 367 l]phenyl} -5,7-dihydro- 1H), 7.72 - 7.50 (m, 2H), 7.47 - 7.32 (m, 1H), 7.34 - (M+H)+
6H-pyrrolo[3,4- 7.16 (m, 2H), 4.86 (t, 7 = 25.0 Hz, 4H), 3.37 (dd, 7 = b]pyridine-6- 14.4, 6.9 Hz, 2H), 2.97 - 2.84 (m, 4H), 1.97 (s, 2H), carboxamide 1.66 - 1.33 (m, 3H), 1.06 - 0.63 (m, 6H)
1201 N-(4-{ [(1 -methyl- 1 H- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.47 (ESI(+)) pyrazol-3- (d, 7 = 4.9 Hz, 1H), 7.84 - 7.70 (m, 3H), 7.70 - 7.55 m/e 377 yl)methyl] carbamoyl } (m, 2H), 7.51 (t, 7 = 5.0 Hz, 1H), 7.32 (dd, 7 = 7.7, 4.9 (M+H)+ phenyl) -5,7 -dihydro- Hz, 1H), 6.15 (d, 7 = 2.2 Hz, 1H), 4.85 (t, 7 = 28.9 Hz,
6H-pyrrolo[3,4- 4H), 4.59 - 4.31 (m, 2H), 3.78 (d, 7 = 4.5 Hz, 3H)
b]pyridine-6- carboxamide
1202 N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.49 (ESI(+)) methoxybutyl)carbamo (d, 7 = 4.9 Hz, 1H), 7.85 (t, 7 = 10.7 Hz, 1H), 7.78 - m/e 369 yl]phenyl}-5,7- 7.69 (m, 2H), 7.68 - 7.49 (m, 2H), 7.43 - 7.30 (m, (M+H)+ dihydro-6H- 1H), 4.86 (t, 7 = 25.0 Hz, 4H), 3.35 (d, 7 = 4.6 Hz,
pyrrolo[3,4-b]pyridine- 2H), 3.32 (d, 7 = 2.7 Hz, 3H), 1.71 - 1.34 (m, 2H),
6-carboxamide 0.90 (t, 7 = 7.4 Hz, 3H)
Figure imgf000733_0001
1212 Ν-{4-[(1- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.47 (ESI(+)) cyanocyclopropyl)carb (d, J = 4.7 Hz, 1H), 7.85 - 7.72 (m, 3H), 7.69 - 7.52 m/e 348 amoyl]phenyl} -5,7- (m, 2H), 7.43 - 7.15 (m, 1H), 4.81 (d, 7 = 11.4 Hz, (M+H)+ dihydro-6H- 4H), 1.61 - 1.41 (m, 2H), 1.40 - 1.17 (m, 2H)
pyrrolo[3,4-b]pyridine- 6-carboxamide
1213 N-(4-{ [2-(5-methyl- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.55 - (ESI(+)) lH-pyrazol-1- 8.36 (m, 1H), 7.87 - 7.75 (m, 1H), 7.75 - 7.67 (m, m/e 391 yl)ethyl] carbamoyl } ph 2H), 7.68 - 7.52 (m, 2H), 7.43 - 7.22 (m, 2H), 6.09 - (M+H)+ enyl) -5,7 -dihydro-6H- 5.92 (m, 1H), 4.91 - 4.64 (m, 4H), 4.36 - 4.10 (m,
pyrrolo[3,4-b]pyridine- 2H), 3.74 - 3.47 (m, 2H), 2.30 - 2.13 (m, 3H)
6-carboxamide
1214 N-(4-{ [(4-methyl-l,3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.59 - (ESI(+)) thiazol-2- 8.31 (m, 1H), 7.92 - 7.72 (m, 3H), 7.71 - 7.58 (m, m/e 394 yl)methyl] carbamoyl } 2H), 7.48 - 7.22 (m, 1H), 7.14 - 6.93 (m, 1H), 4.82 (d, (M+H)+ phenyl) -5,7 -dihydro- 7 = 11.0 Hz, 4H), 4.74 - 4.63 (m, 2H), 2.35 (d, 7 = 0.6
6H-pyrrolo[3,4- Hz, 3H)
b]pyridine-6- carboxamide
1215 N-{4-[(3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.56 - (ESI(+)) hydroxypropyl)carbam 8.38 (m, 1H), 7.88 - 7.79 (m, 1H), 7.79 - 7.68 (m, m/e 341 oyl]phenyl}-5,7- 2H), 7.70 - 7.55 (m, 2H), 7.46 - 7.23 (m, 1H), 4.82 (d, (M+H)+ dihydro-6H- 7 = 9.5 Hz, 4H), 3.51 (t, 7 = 6.3 Hz, 2H), 3.3 (t, 7 = 6.3 pyrrolo[3,4-b]pyridine- Hz, 2H)1.83 - 1.60 (m, 2H)
6-carboxamide
1216 N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.62 - (ESI(+)) methylpropyl)carbamo 8.39 (m, 1H), 7.86 - 7.81 (m, 1H), 7.81 - 7.70 (m, m/e 339 yl]phenyl}-5,7- 2H), 7.70 - 7.54 (m, 2H), 7.43 - 7.17 (m, 1H), 4.84 (M+H)+ dihydro-6H- (dd, 7 = 30.5, 23.8 Hz, 4H), 3.17 - 3.01 (m, 2H), 2.03 pyrrolo[3,4-b]pyridine- - 1.72 (m, 2H), 0.89 (t, 7 = 7.9 Hz, 6H)
6-carboxamide
1217 N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.57 - (ESI(+))
[(tetrahydrofuran-2 - 8.39 (m, 1H), 7.86 - 7.80 (m, 1H), 7.80 - 7.69 (m, m/e 367 ylmethyl)carbamoyl]p 2H), 7.69 - 7.54 (m, 2H), 7.42 - 7.26 (m, 1H), 4.82 (d, (M+H)+ henyl } -5 ,7 -dihydro- 7 = 10.1 Hz, 4H), 4.12 - 3.93 (m, 1H), 3.88 - 3.75 (m,
6H-pyrrolo[3,4- 1H), 3.74 - 3.54 (m, 1H), 3.33 (t, 7 = 5.9 Hz, 2H),
b]pyridine-6- 1.98 - 1.78 (m, 4H), 1.71 - 1.51 (m, 1H)
carboxamide
1218 N-(4-{ [(lR)-l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.49 (t, (ESI(+)) cyclopropylethyl] carba 7 = 5.8 Hz, 1H), 7.90 - 7.80 (m, 1H), 7.80 - 7.69 (m, m/e 351 moyl } phenyl)-5 ,7 - 2H), 7.68 - 7.54 (m, 2H), 7.36 (dd, 7 = 7.7, 5.0 Hz, (M+H)+ dihydro-6H- 1H), 4.82 (d, 7 = 9.6 Hz, 4H), 3.64 - 3.41 (m, 1H),
pyrrolo[3,4-b]pyridine- 1.23 (d, 7 = 6.7 Hz, 3H), 1.10 - 0.86 (m, 1H), 0.53 - 6-carboxamide 0.28 (m, 3H), 0.28 - 0.11 (m, 1H)
1219 N-(4-{ [l-(l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.60 - (ESI(+)) methylcyclopropyl)eth 8.35 (m, 1H), 7.93 - 7.79 (m, 1H), 7.79 - 7.68 (m, m/e 365 yl]carbamoyl jphenyl)- 2H), 7.68 - 7.53 (m, 2H), 7.49 - 7.22 (m, 1H), 4.82 (d, (M+H)+
5,7-dihydro-6H- 7 = 9.2 Hz, 4H), 3.72 (q, 7 = 6.8 Hz, 1H), 1.17 (d, 7 =
pyrrolo[3,4-b]pyridine- 6.8 Hz, 3H), 1.08 (s, 3H), 0.67 - 0.48 (m, 1H), 0.47 -
6-carboxamide 0.34 (m, 1H), 0.32 - 0.12 (m, 2H)
1220 N-{4-[(thiophen-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.45 (t, (ESI(+)) ylmethyl)carbamoyl]p 7 = 8.3 Hz, 1H), 7.83 - 7.71 (m, 3H), 7.68 - 7.55 (m, m/e 379 henyl } -5 ,7 -dihydro- 2H), 7.39 - 7.21 (m, 1H), 7.08 - 6.98 (m, 1H), 6.99 - (M+H)+ 6H-pyrrolo[3,4- 6.90 (m, 1H), 4.80 (d, 7 = 12.9 Hz, 4H), 4.63 (s, 2H) b]pyridine-6- carboxamide
1221 N-(4-{ [(lS)-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.49 (ESI(+)) cyclopropylethyl] carba (d, J = 4.9 Hz, 1H), 7.85 (d, 7 = 7.7 Hz, 1H), 7.78 - m/e 350 moyl } phenyl)-5 ,7 - 7.69 (m, 2H), 7.72 - 7.54 (m, 2H), 7.37 (dd, 7 = 7.7, (M+H)+ dihydro-6H- 5.0 Hz, 1H), 4.96 - 4.68 (m, 4H), 3.70 - 3.42 (m, 1H), pyrrolo[3,4-b]pyridine- 1.23 (d, 7 = 6.7 Hz, 3H), 1.15 - 0.90 (m, 1H), 0.58 - 6-carboxamide 0.16 (m, 4H)
1222 N-{4-[(4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.60 - (ESI(+)) methoxybutyl)carbamo 8.35 (m, 1H), 7.90 - 7.79 (m, 1H), 7.79 - 7.70 (m, m/e 369 yl]phenyl}-5,7- 2H), 7.69 - 7.52 (m, 2H), 7.43 - 7.29 (m, 1H), 4.86 (t, (M+H)+ dihydro-6H- 7 = 24.4 Hz, 4H), 3.31 - 3.25 (m, 2H), 2.68 - 2.34 (m, pyrrolo[3,4-b]pyridine- 2H), 1.65 - 1.48 (m, 4H)
6-carboxamide
1223 N-(4-{ [2-(tetrahydro- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.55 - (ESI(+))
2H-pyran-3- 8.37 (m, 1H), 7.89 - 7.78 (m, 1H), 7.78 - 7.68 (m, m/e 395 yl)ethyl] carbamoyl } ph 2H), 7.68 - 7.52 (m, 2H), 7.43 - 7.02 (m, 1H), 4.86 (t, (M+H)+ enyl) -5,7 -dihydro-6H- 7 = 25.4 Hz, 4H), 3.96 - 3.57 (m, 2H), 3.12 - 2.98 (m, pyrrolo[3,4-b]pyridine- 1H), 2.95 - 2.78 (m, 2H), 1.91 - 1.76 (m, 1H), 1.63 - 6-carboxamide 1.40 (m, 4H), 1.28 - 1.09 (m, 1H)
1224 N-(4-{ [(2S)-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.58 - (ESI(+)) methoxypropan-2- 8.40 (m, 1H), 7.87 - 7.81 (m, 1H), 7.80 - 7.72 (m, m/e 355 yl]carbamoyl jphenyl)- 2H), 7.69 - 7.51 (m, 2H), 7.34 (dd, 7 = 7.7, 5.0 Hz, (M+H)+
5,7-dihydro-6H- 1H), 4.81 (d, 7 = 11.0 Hz, 4H), 4.30 - 4.08 (m, 1H), pyrrolo[3,4-b]pyridine- 3.49 - 3.42 (m, 1H), 3.40 - 3.33 (m, 1H), 3.29 (s, 3H),
6-carboxamide 1.16 (1, 7 = 5.4 Hz, 3H)
1225 N-{4-[(3,3-dimethyl-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.49 (ESI(+)) oxobutyl)carbamoyl]p (d, 7 = 4.3 Hz, 1H), 7.89 - 7.81 (m, 1H), 7.84 - 7.73 m/e 391 henyl } -5 ,7 -dihydro- (m, 2H), 7.74 - 7.56 (m, 2H), 7.44 - 7.18 (m, 1H), (M+H)+
6H-pyrrolo[3,4- 4.83 (d, 7 = 9.2 Hz, 4H), 4.30 (s, 2H), 1.18 (s, 9H)
b]pyridine-6- carboxamide
1226 N-(4-{ [(1 -methyl- 1H- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.58 - (ESI(+)) pyrrol-2- 8.35 (m, 1H), 7.92 - 7.71 (m, 3H), 7.70 - 7.49 (m, m/e 376 yl)methyl] carbamoyl } 2H), 7.44 - 7.19 (m, 1H), 4.82 (d, 7 = 9.5 Hz, 4H), (M+H)+ phenyl) -5,7 -dihydro- 4.44 (s, 2H), 3.59 (s, 3H)
6H-pyrrolo[3,4- b]pyridine-6- carboxamide
1227 N-(4-{ [2-(propan-2- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.60 - (ESI(+)) yloxy)ethyl] carbamoyl 8.37 (m, 1H), 7.86 - 7.72 (m, 3H), 7.71 - 7.56 (m, m/e 369
}phenyl)-5,7-dihydro- 3H), 7.47 - 7.19 (m, 1H), 4.87 - 4.66 (m, 4H), 3.67 - (M+H)+
6H-pyrrolo[3,4- 3.48 (m, 3H), 3.42 - 3.36 (m, 2H), 1.16 - 1.02 (m, 6H) b]pyridine-6- carboxamide
1228 N-(4-{ [3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.59 - (ESI(+))
(dimethylamino)propyl 8.13 (m, 1H), 7.91 - 7.72 (m, 3H), 7.73 - 7.58 (m, m/e 368 ]carbamoyl jphenyl)- 2H), 7.43 - 7.26 (m, 1H), 4.83 (t, 7 = 9.4 Hz, 4H), (M+H)+ 5,7-dihydro-6H- 3.37 (d, 7 = 6.7 Hz, 2H), 3.27 - 3.07 (m, 2H), 2.81 (d, pyrrolo[3,4-b]pyridine- 7 = 4.7 Hz, 6H), 1.95 (d, 7 = 9.3 Hz, 2H)
6-carboxamide 1229 N-[4-(tetrahydro-2H- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.56 - (ESI(+)) pyran-3- 8.35 (m, 1H), 7.90 - 7.68 (m, 3H), 7.69 - 7.56 (m, m/e 367 ylcarbamoyl)phenyl] - 2H), 7.36 (td, J = 7.9, 4.0 Hz, 1H), 4.82 (d, 7 = 10.2 (M+H)+ 5,7-dihydro-6H- Hz, 4H), 3.99 - 3.86 (m, 1H), 3.86 - 3.68 (m, 1H),
pyrrolo[3,4-b]pyridine- 3.41 - 3.32 (m, 1H), 3.29 - 3.17 (m, 1H), 2.07 - 1.84
6-carboxamide (m, 1H), 1.83 - 1.50 (m, 3H)
1230 N-(4-{ [2-(lH-pyrrol-l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.56 - (ESI(+)) yl)ethyl] carbamoyl } ph 8.30 (m, 1H), 7.87 - 7.76 (m, 1H), 7.76 - 7.65 (m, m/e 376 enyl) -5,7 -dihydro-6H- 2H), 7.67 - 7.50 (m, 2H), 7.41 - 7.20 (m, 1H), 6.73 (t, (M+H)+ pyrrolo[3,4-b]pyridine- 7 = 2.0 Hz, 1H), 6.17 - 5.79 (m, 1H), 4.86 - 4.72 (m,
6-carboxamide 4H), 4.08 (t, 7 = 6.5 Hz, 2H), 3.57 (t, 7 = 6.5 Hz, 2H)
1231 N-{4-[(l- ¾ NMR (400 MHz, DMSO-<¾, Temp=90°C) δ 8.49 (ESI(+)) methoxypropan-2- (d, 7 = 4.8 Hz, 1H), 7.85 (t, 7 = 8.8 Hz, 1H), 7.81 - m/e 355 yl)carbamoyl]phenyl } - 7.70 (m, 2H), 7.70 - 7.52 (m, 2H), 7.51 - 7.22 (m, (M+H)+
5,7-dihydro-6H- 1H), 4.82 (d, 7 = 9.0 Hz, 4H), 4.19 (h, 7 = 6.6 Hz, 1H), pyrrolo[3,4-b]pyridine- 3.59 - 3.43 (m, 1H), 3.30 (s, 3H), 2.88 (d, 7 = 50.6 Hz,
6-carboxamide 1H), 1.15 (dd, 7 = 10.7, 6.7 Hz, 3H)
1232 N-{4-[(3- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.48 (ESI(+)) aminobenzyl)carbamo (d, 7 = 4.7 Hz, 1H), 7.92 - 7.76 (m, 3H), 7.74 - 7.51 m/e 388 yl]phenyl}-5,7- (m, 2H), 7.32 (ddd, 7 = 15.4, 7.7, 4.6 Hz, 2H), 7.18 - (M+H)+ dihydro-6H- 7.08 (m, 2H), 7.00 (d, 7 = 7.9 Hz, 1H), 4.82 (d, 7 =
pyrrolo[3,4-b]pyridine- 11.2 Hz, 4H), 4.47 (s, 2H)
6-carboxamide
1233 N-(4-{ [(2R)-3- ¾ NMR (400 MHz, DMSO_D20) δ 8.56 - 8.39 (m, (ESI(+)) methylbutan-2- 1H), 7.92 - 7.80 (m, 1H), 7.80 - 7.68 (m, 2H), 7.68 - m/e 353 yl]carbamoyl jphenyl)- 7.53 (m, 2H), 7.53 - 6.97 (m, 1H), 4.83 (d, 7 = 7.2 Hz, (M+H)+
5,7-dihydro-6H- 4H), 3.99 - 3.74 (m, 1H), 1.91 - 1.66 (m, 1H), 1.12 (d, pyrrolo[3,4-b]pyridine- 7 = 6.8 Hz, 3H), 0.99 - 0.82 (m, 6H)
6-carboxamide
1234 N- { 4- [(tetrahydro-2H- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.62 - (ESI(+)) pyran-3- 8.38 (m, 1H), 7.91 - 7.80 (m, 1H), 7.80 - 7.70 (m, m/e 381 ylmethyl)carbamoyl]p 2H), 7.69 - 7.45 (m, 2H), 7.48 - 7.24 (m, 1H), 4.83 (d, (M+H)+ henyl } -5 ,7 -dihydro- 7 = 8.0 Hz, 4H), 3.87 - 3.61 (m, 2H), 3.19 - 3.12 (m,
6H-pyrrolo[3,4- 3H), 1.92 (d, 7 = 34.0 Hz, 1H), 1.87 - 1.73 (m, 2H), b]pyridine-6- 1.67 - 1.55 (m, 1H), 1.55 - 1.37 (m, 1H), 1.39 - 1.14 carboxamide (m, 1H)
1235 N-{4-[(2-hydroxy-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.61 - (ESI(+)) methylpropyl)carbamo 8.43 (m, 1H), 7.90 - 7.71 (m, 3H), 7.71 - 7.50 (m, m/e 355 yl]phenyl}-5,7- 2H), 7.42 - 7.14 (m, 1H), 4.98 - 4.68 (m, 4H), 3.04 - (M+H)+ dihydro-6H- 2.66 (m, 2H), 1.29 - 1.01 (m, 6H)
pyrrolo[3,4-b]pyridine-
6-carboxamide
1236 N-[4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.55 - (ESI(+))
(butylcarbamoyl)phen 8.42 (m, 1H), 7.85 - 7.77 (m, 1H), 7.79 - 7.68 (m, m/e 339 yl]-5,7-dihydro-6H- 2H), 7.68 - 7.54 (m, 2H), 7.47 - 6.86 (m, 1H), 4.80 (t, (M+H)+ pyrrolo[3,4-b]pyridine- 7 = 9.0 Hz, 4H), 3.26 - 3.17 (m, 2H), 1.63 - 1.49 (m,
6-carboxamide 2H), 1.46 - 1.27 (m, 2H), 0.92 (dd, 7 = 9.2, 5.5 Hz,
3H)
1237 N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.57 - (ESI(+))
[methyl(tetrahydrofura 8.37 (m, 1H), 7.90 - 7.72 (m, 1H), 7.66 - 7.52 (m, m/e 381 n-2- 2H), 7.45 - 7.34 (m, 1H), 7.33 - 7.16 (m, 2H), 4.86 (t, (M+H)+ ylmethyl)carbamoyl]p 7 = 24.4 Hz, 4H), 4.21 - 3.97 (m, 1H), 3.86 - 3.55 (m, henyl } -5 ,7 -dihydro- 2H), 3.57 - 3.39 (m, 2H), 3.08 - 2.97 (m, 3H), 1.98 - 6H-pyrrolo[3,4- 1.88 (m, 2H), 1.85 - 1.68 (m, 2H), 1.60 - 1.37 (m, 1H) b]pyridine-6- carboxamide
1238 N-{4-[(2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.49 (t, (ESI(+)) methoxyethyl) (methyl) J = 5.2 Hz, 1H), 7.95 - 7.76 (m, 1H), 7.71 - 7.52 (m, m/e 355 carbamoyl]phenyl } - 2H), 7.38 - 7.33 (m, 1H), 7.33 - 7.22 (m, 2H), 4.82 (d, (M+H)+ 5,7-dihydro-6H- 7 = 9.0 Hz, 4H), 3.61 - 3.44 (m, 4H), 3.29 - 3.19 (m, pyrrolo[3,4-b]pyridine- 3H), 2.98 (s, 3H)
6-carboxamide
1239 N-{4-[(l- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.59 - (ESI(+)) cyanoethyl)carbamoyl] 8.32 (m, 1H), 7.91 - 7.72 (m, 3H), 7.72 - 7.59 (m, m/e 336 phenyl } -5,7-dihydro- 2H), 7.40 - 7.20 (m, 1H), 5.03 - 4.86 (m, 1H), 4.88 - (M+H)+ 6H-pyrrolo[3,4- 4.68 (m, 4H), 1.72 - 1.43 (m, 3H)
b]pyridine-6- carboxamide
1240 N-{4-[(3R)- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.48 (ESI(+)) tetrahydrofuran-3- (d, 7 = 4.4 Hz, 1H), 7.89 - 7.74 (m, 3H), 7.68 - 7.48 m/e 353 ylcarbamoyl]phenyl}- (m, 2H), 7.45 - 7.24 (m, 1H), 4.82 (d, 7 = 9.2 Hz, 4H), (M+H)+
5,7-dihydro-6H- 4.59 - 4.28 (m, 1H), 3.94 - 3.83 (m, 2H), 3.80 - 3.64 pyrrolo[3,4-b]pyridine- (m, 1H), 3.65 - 3.51 (m, 1H), 2.37 - 2.00 (m, 1H),
6-carboxamide 2.05 - 1.80 (m, 1H)
1241 N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.49 (ESI(+))
[(cyclopentylmethyl)ca (d, 7 = 4.8 Hz, 1H), 7.90 - 7.80 (m, 1H), 7.80 - 7.68 m/e 365 rbamoyl]phenyl } -5,7- (m, 2H), 7.68 - 7.49 (m, 2H), 7.47 - 7.11 (m, 1H), (M+H)+ dihydro-6H- 4.82 (d, 7 = 9.0 Hz, 4H), 3.26 - 3.10 (m, 2H), 2.36 - pyrrolo[3,4-b]pyridine- 2.07 (m, 1H), 1.75 - 1.45 (m, 6H), 1.39 - 1.18 (m, 2H)
6-carboxamide
1242 N-{4-[(2-methoxy-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.61 - (ESI(+)) methylpropyl)carbamo 8.36 (m, 1H), 7.88 - 7.71 (m, 3H), 7.71 - 7.55 (m, m/e 369 yl]phenyl}-5,7- 2H), 7.46 - 7.15 (m, 1H), 4.99 - 4.66 (m, 4H), 3.35 (d, (M+H)+ dihydro-6H- 7 = 4.5 Hz, 2H), 3.19 - 3.16 (m, 3H), 1.46 - 0.84 (m, pyrrolo[3,4-b]pyridine- 6H)
6-carboxamide
1243 N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.60 - (ESI(+))
[(cyclopropylmethyl)c 8.40 (m, 1H), 7.85 (d, 7 = 7.7 Hz, 1H), 7.82 - 7.71 (m, m/e 337 arbamoyl]phenyl } -5,7- 2H), 7.71 - 7.53 (m, 2H), 7.38 (dd, 7 = 7.7, 5.0 Hz, (M+H)+ dihydro-6H- 1H), 7.30 - 7.14 (m, 1H), 5.07 - 4.65 (m, 4H), 3.16 (t, pyrrolo[3,4-b]pyridine- 7 = 6.6 Hz, 2H), 1.20 - 0.87 (m, 1H), 0.52 - 0.37 (m,
6-carboxamide 2H), 0.32 - 0.06 (m, 2H)
1244 N-{4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.61 - (ESI(+))
[methyl(propyl)carbam 8.38 (m, 1H), 7.93 - 7.76 (m, 1H), 7.68 - 7.54 (m, m/e 339 oyl]phenyl}-5,7- 2H), 7.46 - 7.33 (m, 1H), 7.31 - 7.17 (m, 2H), 4.97 - (M+H)+ dihydro-6H- 4.59 (m, 4H), 2.92 (d, 7 = 8.0 Hz, 4H), 1.67 - 1.47 (m, pyrrolo[3,4-b]pyridine- 2H), 0.96 - 0.59 (m, 3H)
6-carboxamide
1245 N-{4-[(pyridin-4- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 8.83 - (ESI(+)) ylmethyl)carbamoyl]p 8.62 (m, 2H), 8.52 - 8.39 (m, 1H), 7.96 - 7.77 (m, m/e 374 henyl } -5 ,7 -dihydro- 3H), 7.77 - 7.70 (m, 2H), 7.70 - 7.59 (m, 2H), 7.43 - (M+H)+
6H-pyrrolo[3,4- 7.14 (m, 1H), 4.90 - 4.72 (m, 4H), 4.74 - 4.48 (m, 2H) b]pyridine-6- carboxamide
Example 293
N-{4-[(4-phenylbutanoyl)amino]phenyl} -l,3-dihydro-2H-isoindole-2-carboxamide Example 293A
N-(4-nitrophenyl)isoindoline-2-carboxamide
A solution of N-(4-aminophenyl)isoindoline-2-carboxamide (100 mg, 0.395 mmol), 4-phenylbutanoic acid (78 mg, 0.474 mmol), 1-hydroxybenzotriazole hydrate (66.5 mg, 0.434 mmol) and N-methylmorpholine (0.109 ml, 0.987 mmol) in N,N-dimethylformamide (1.771 ml) at room temperature was treated with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (136 mg, 0.711 mmol). The mixture was stirred overnight and diluted with water (10 ml); the resulting suspension was filtered with water washes to give after drying product with an impurity. This solid was suspended in 2% methanol/dichloromethane and filtered to provide the title compound.
Example 293B
N-(4-aminophenyl)isoindoline-2-carboxamide
The title compound was prepared as described in Example 274, substituting N-(4- nitrophenyl)isoindoline-2-carboxamide for 5-nitro-N-[4-(propylcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide.
Example 293C
N-{4-[(4-phenylbutanoyl)amino]phenyl}-l,3-dmydro-2H-isoindole-2-carboxarnide A solution of N-(4-aminophenyl)isoindoline-2-carboxarnide (100 mg, 0.395 mmol), 4-phenylbutanoic acid (78 mg, 0.474 mmol), 1-hydroxybenzotriazole hydrate (66.5 mg, 0.434 mmol) and N-methylmorpholine (0.109 ml, 0.987 mmol) in dimethylformamide (1.771 ml) at room temperature was treated with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (136 mg, 0.711 mmol). The mixture was stirred overnight and diluted with water (10 ml); the resulting suspension was filtered with water washes to give product with an impurity. This solid was suspended in 2% methanol/methylene chloride and filtered to provide the title compound. ¾ NMR (300 MHz, DMSO-d6) δ ppm 1.78 - 2.00 (m, 2 H), 2.30 (t, 7=7.3 Hz, 2 H), 2.62 (t, 7=7.5 Hz, 2 H), 4.75 (s, 4 H), 7.08 - 7.41 (m, 9 H), 7.46 (s, 4 H), 8.26 (s, 1 H), 9.73 (s, 1 H); (ESI(+)) m/e 400 (M+H)+.
Table 5.
The following Examples were prepared essentially as described in Example 293, using an appropriate amine in Example 293A and substituting an appropriate carboxylic acid for 4-phenylbutanoic acid in Example 293C. Some products were purified by flash chromatography while others were purified by reverse-phase HPLC; accordingly, some Examples were isolated as trifluoroacetic acid salts.
Figure imgf000738_0001
Figure imgf000739_0001
303 N-[4- ¾ NMR (400 MHz, DMSO-^ Deuterium (ESI(+))
Figure imgf000740_0001
Figure imgf000741_0001
Figure imgf000742_0001
carboxamide 1.68 - 1.43 (m, 4H), 1.26 - 1.10 (m, 2H)
Example 313
methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylate Example 313A
methyl 2-(4-nitrophenylcarbamoyl)isoindoline-5-carboxylate The title compound was prepared as described in Example 1A, substituting 4- nitrophenyl isocyanate for methyl 4-isocyanatobenzoate and methyl isoindoline-5-carboxylate hydrochloride for isoindoline.
Example 313B
methyl 2-(4-aminophenylcarbamoyl)isoindoline-5-carboxylate The title compound was prepared as described in Example 274, substituting methyl 2- (4-nittophenylcarbamoyl)isoindoline-5-carboxylate for 5-nitro-N-[4- (propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide.
Example 313C
methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylate The title compound was prepared as described in Example 278, substituting methyl 2- (4-aminophenylcarbamoyl)isoindoline-5-carboxylate for 5-amino-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide and 2-cyclopentylacetyl chloride for acetyl chloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.69 (s, IH), 8.32 (s, IH), 7.94-7.94 (m, IH), 7.89-7.96 (m, IH), 7.51 (d, J = 8.1 Hz, IH), 7.41-7.49 (m, 4H), 4.75-4.82 (m, 4H), 3.87 (s, 3H), 2.24-2.29 (m, 2H), 2.15-2.28 (m, IH), 1.68-1.81 (m, 2H), 1.44-1.67 (m, 4H), 1.13-1.24 (m, 2H); MS (ESI(+)) m/e 422 (M+H)+.
Example 314
2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid The title compound was prepared as described in Example IB, substituting methyl 2- ({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylate for methyl 4- (isoindoline-2-carboxamido)benzoate. ¾ NMR (300 MHz, DMSO- ) δ ppm 12.97 (dd, J = 4.1, 2.1 Hz, IH), 9.70 (s, IH), 8.32 (s, IH), 7.88-7.92 (m, 2H), 7.46-7.50 (m, IH), 7.43-7.48 (m, 4H), 4.79-4.81 (bs, 4H), 2.24-2.30 (m, 2H), 2.16-2.29 (m, IH), 1.68-1.81 (m, 2H), 1.44- 1.67 (m, 4H), 1.10-1.27 (m, 2H); MS (ESI(-)) m/e 406 (M-H)\
Example 315
N- { 4-[(cyclopentylacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
To a stirring suspension of 2-(4-(2- cyclopentylacetamido)phenylcarbamoyl)isoindoline-5-carboxylic acid (18 mg, 0.044 mmol) in tetrahydrofuran was added 1M borane in tetrahydrofuran (0.18 mL, 0.18 mml) dropwise. The mixture was heated at 60°C for 1 hour. The reaction was cooled to room temperature and treated with several drops of 4M HCl-dioxane and methanol and then the clear solution was stirred at room temperature for 2 hours. The reaction was concentrated and purified by reverse- phase HPLC to provide the title compound. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.69 (s, 1H), 8.26 (s, 1H), 7.45 (s, 4H), 7.28-7.32 (m, 2H), 7.22-7.26 (m, 1H), 5.18-5.22 (m, 1H), 4.72-4.73 (bs, 4H), 4.50-4.53 (bs, 2H), 2.17-2.32 (m, 3H), 1.70-1.80 (m, 2H), 1.44-1.67 (m, 4H), 1.13-1.24 (m, 2H); MS (ESI(+)) m/e 394 (M+H)+.
Example 316
N-{4-[(2-cyclopentylethyl)amino]phenyl}-5-(hydroxymethyl)-13-dihydro-2H-isoindole-2- carboxamide
To a stirring suspension of 2-(4-(2- cyclopentylacetamido)phenylcarbamoyl)isoindoline-5-carboxylic acid (18 mg, 0.044 mmol) in tetrahydrofuran was added 1M borane in tetrahydrofuran (0.18 mL, 0.18 mml) dropwise. The mixture was heated at 60°C for 1 hour. The reaction was cooled to room temperature and treated with several drops of 4M HCl-dioxane and methanol and then the clear solution was stirred at room temperature for 2 hours. The reaction was concentrated and purified by reverse- phase HPLC to provide the title compound. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.92 (s, 1H), 7.27-7.31 (m, 2H), 7.24 (d, J = 8.1 Hz, 1H), 7.15-7.20 (m, 2H), 6.45-6.51 (m,
2H), 5.17-5.21 (m, 2H), 4.68-4.69 (bs, 4H), 4.51 (d, J = 5.4 Hz, 2H), 2.97 (q, J = 6.7 Hz, 2H), 1.70-1.95 (m, 3H), 1.42-1.66 (m, 6H), 1.04-1.20 (m, 2H); MS (ESI(+)) m/e 380 (M+H)+.
Example 317
tert-Butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6-dihydropyridine- l(2H)-carboxylate
Example 317A
N-(4-bromophenyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 1A, substituting 4- bromophenyl isocyanate for methyl 4-isocyanatobenzoate.
Example 317B
tert- butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6-dihydropyridine-
1 (2H)-carboxylate
The title compound was prepared as described in Example 280, substituting tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate for lH-pyrazol-3-ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo- N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.38 (s, 1H), 7.55-7.57 (m, 2H), 7.26-7.42 (m, 6H), 6.06-6.09 (bs, 1H), 4.76-4.77 (bs, 4H), 3.97-4.00 (m, 2H), 3.51-3.55 (m, 2H), 2.42-2.46 (m, 2H), 1.43 (s, 9H); MS (ESI(-)) m/e 418 (M-H)\
Example 318
N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-{4-[(1 -dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl}-3,6-dmydropyridine-l(2H)- carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate. ¾ NMR (400 MHz, DMSO-iie) δ ppm 8.44 (s, IH), 7.58-7.61 (m, 2H), 7.30-7.41 (m, 6H), 6.12-6.14 (bs, IH), 4.77-4.78 (bs, 4H), 3.70-3.72 (m, 2H), 3.27-3.31 (m, 2H), 2.60-2.64 (m, 2H); MS (ESI(+)) m/e 320 (M+H)+.
Example 319
N-{ 4-[l -(3-methylbutyl)- lH-pyrazol-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 1- isopentyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3- ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 0.91 (d, 7=6.4 Hz, 6 H), 1.40 - 1.60 (m, 1 H), 1.70 (q, 7=6.8 Hz, 2 H), 4.11 (t, 7=7.1 Hz, 2 H), 4.77 (s, 4 H), 7.13 - 7.40 (m, 4 H), 7.42 - 7.50 (m, 2 H), 7.50 - 7.61 (m, 2 H), 7.78 (s, 1 H), 8.08 (s, 1 H), 8.32 (s, 1 H); MS (ESI(+)) m/e 375 (M+H)+.
Example 320
N- [4-( 1 -methyl- 1 H-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 1-methyl- 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 3.84 (s, 3 H), 4.77 (s, 4 H), 7.24 - 7.40 (m, 4 H), 7.40 - 7.49 (m, 2 H), 7.50 - 7.60 (m, 2 H), 7.77 (s, 1 H), 8.02 (s, 1 H), 8.33 (s, 1 H); MS (ESI(+)) m/e 319 (M+H)+.
Example 321
N- { 4- [( 1 E) -5 -phenylpent- 1 -en- 1 -yl] phenyl } - 1 , 3 -dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 280, substituting (E)- 4,4,5,5 -tetramethyl-2-(5 -phenylpent- l-enyl)-l, 3, 2-dioxaborolane for lH-pyrazol-3-ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 1.60 - 1.84 (m, 2 H), 2.19 (q, 7=7.0 Hz, 2 H), 2.55 - 2.71 (m, 2 H), 4.76 (s, 4 H), 6.12 - 6.27 (m, 1 H), 6.26 - 6.43 (m, 1 H), 7.09 - 7.44 (m, 11 H), 7.52 (d, 7=8.5 Hz, 2 H), 8.33 (s, 1 H); MS (ESI(+)) m/e 383 (M+H)+.
Example 322
N- [4-( 1 -propyl- 1 H-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 1-propyl-
4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 0.85 (t, 7=7.3 Hz, 3 H), 1.69 - 1.93 (m, 2 H), 4.05 (t, 7=6.9 Hz, 2 H), 4.77 (s, 4 H), 7.26 - 7.40 (m, 4 H), 7.42 - 7.49 (m, 2 H), 7.52 - 7.61 (m, 2 H), 7.79 (s, 1 H), 8.07 (s, 1 H), 8.33 (s, 1 H); MS (ESI(+)) m/e 347 (M+H)+.
Example 323
N- [4-( 1 -benzyl- 1 H-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The tide compound was prepared as described in Example 280, substituting 1 -benzyl -
4- (4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 4.77 (s, 4 H), 5.33 (s, 2 H), 7.21 - 7.42 (m, 9 H), 7.41 - 7.51 (m, 2 H), 7.51 - 7.61 (m, 2 H), 7.84 (s, 1 H), 8.17 (s, 1 H), 8.33 (s, 1 H); MS (ESI(+)) m/e 395 (M+H)+.
Example 324
N- { 4- [ 1 -(2-hydroxyethyl)- lH-pyrazol-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 2-(4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl)ethanol for lH-pyrazol-3- ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 3.76 (q, 7=5.8 Hz, 2 H), 4.14 (t, 7=5.6 Hz, 2 H), 4.77 (s, 4 H), 4.90 (t, 7=5.4 Hz, 1 H), 7.25 - 7.41 (m, 4 H), 7.41 - 7.51 (m, 2 H), 7.51 - 7.60 (m, 2 H), 7.80 (s, 1 H), 8.04 (s, 1 H), 8.32 (s, 1 H); MS (ESI(+)) m/e 349 (M+H)+.
Example 325
N-[6-(l -propyl- lH-pyrazol-4-yl)pyridin-3-yl]-l,3-dmydro-2H-isoindole-2-carboxarnide
Example 325A
N-(6-chloropyridin-3-yl)isoindoline-2-carboxamide The title compound was prepared as described in Example 1A, substituting 2-chloro-
5- isocyanatopyridine for methyl 4-isocyanatobenzoate.
Example 325B
N-[6-(l -propyl- lH-pyrazol-4-yl)pyridin-3-yl]-l,3-dmydro-2H-isoindole-2-carboxarnide
The title compound was prepared as described in Example 280, substituting 1-propyl- 4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid and N-(6-chloropyridin-3-yl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.90-8.92 (bs, 1H), 8.84 (d, 7 = 2.5 Hz, 1H), 8.39 (s, 1H), 8.25 (dd, 7 = 8.8, 2.5 Hz, 1H), 8.08 (s, 1H), 7.87 (d, 7 = 8.8 Hz, 1H), 7.31-7.41 (m, 4H), 4.79-4.83 (bs, 4H), 4.13 (t, J = 6.9 Hz, 2H), 1.77-1.89 (m, 2H), 0.86 (t, 7 = 7.3 Hz, 3H); MS (ESI(+)) m/e 348 (M+H)+.
Example 326
N- { 6- [ 1 -(3-methylbutyl)- 1 H-pyrazol-4-yl]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The tide compound was prepared as described in Example 280, substituting 1- isopentyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)- lH-pyrazole for lH-pyrazol-3- ylboronic acid and N-(6-chloropyridin-3-yl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.85-8.87 (bs, 1H), 8.81 (d, 7 = 2.5 Hz, 1H), 8.38 (s, 1H), 8.21 (dd, 7 = 8.8, 2.5 Hz, 1H), 8.05 (s, 1H), 7.82 (d, 7 = 8.8 Hz, 1H), 7.31-7.41 (m, 4H), 4.78-4.83 (bs, 4H), 4.19 (t, 7 = 7.1 Hz, 2H), 1.71 (q, 7 = 7.0 Hz, 2H), 1.40-1.59 (m, 1H), 0.92 (d, 7 = 6.6 Hz, 6H); MS (ESI(-)) m/e 374 (M-H)\
Example 327
N-[4-(5-phenylpentyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 274, substituting N-{4- [(lE)-5-phenylpent- 1 -en- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide for 5-nitro- N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 1.21 - 1.40 (m, 4 H), 1.49 - 1.67 (m, 4 H), 2.45 - 2.62 (m, 2 H), 4.75 (s, 4 H), 7.05 (d, 7=8.7 Hz, 2 H), 7.14 - 7.40 (m, 9 H), 7.44 (d, 7=8.3 Hz, 2 H), 8.23 (s, 1 H); MS (ESI(+)) m/e 385 (M+H)+.
Example 328
N- [2-fluoro-4-( 1 -propyl- 1 H-pyrazol-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2-carboxamide
Example 328A
N-(4-bromo-2-fluorophenyl)isoindoline-2-carboxamide
The title compound was prepared as described in Example 1A, substituting 4-bromo- 2-fluoro-l-isocyanatobenzene for methyl 4-isocyanatobenzoate.
Example 328B
N- [2-fluoro-4-( 1 -propyl- 1 H-pyrazol-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 1-propyl-
4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid and N-(4-bromo-2-fluorophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.19 (s, 1H), 8.03 (s, 1H), 7.89 (s, 1H), 7.57 (t, 7 = 8.4 Hz, 1H), 7.46 (dd, 7 = 12.1, 1.9 Hz, 1H), 7.24-7.39 (m, 5H), 4.76-4.78 (bs, 4H), 4.06 (t, 7 = 6.9 Hz, 2H), 1.75-1.88 (m, 2H), 0.86 (t, 7 = 7.3 Hz, 3H); MS (ESI(+)) m/e 365 (M+H)+. Example 329
N-{2-fluoro-4-[l-(3-memylbutyl)-lH-^
carboxamide
The tide compound was prepared as described in Example 280, substituting 1- isopentyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)- lH-pyrazole for lH-pyrazol-3- ylboronic acid and N-(4-bromo-2-fluorophenyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.21 (s, IH), 8.04 (s, IH), 7.88 (s, IH), 7.56 (t, 7 = 8.4 Hz, IH), 7.46 (dd, 7 = 12.1, 1.9 Hz, IH), 7.25-7.41 (m, 5H), 4.76-4.81 (m, 4H), 4.12 (t, 7 = 7.2 Hz, 2H), 1.70 (q, 7 = 7.1 Hz, 2H), 1.40-1.59 (m, IH), 0.91 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 393 (M+H)+.
Example 330
N-[4-(l-butyryl-l ,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting butyryl chloride for acetyl chloride and N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.38 (s, IH), 7.55-7.58 (m, 2H), 7.27- 7.38 (m, 6H), 6.09-6.11 (m, IH), 4.77 (s, 4H), 4.08-4.14 (m, 2H), 3.58-3.68 (m, 2H), 2.39- 2.51 (m, 2H), 2.34 (dt, 7 = 19.8, 7.3 Hz, 2H), 1.46-1.62 (m, 2H), 0.88-0.93 (m, 3H); MS (ESI(+)) m/e 390 (M+H)+.
Example 331
N- [4-( 1 -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting isobutyryl chloride for acetyl chloride and N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide for 5-amino-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (500 MHz, DMSO-iie) δ ppm 8.40 (s, IH), 7.55-7.58 (m, 2H), 7.30-7.38 (m, 6H), 6.11 -6.13 (bs, IH), 4.76-4.77 (bs, 4H), 4.19-4.21 (m, IH), 4.08-4.09 (m, IH), 3.65-3.72 (m, 2H), 2.85-3.00 (m, IH), 2.40-2.56 (m, 2H), 1.00- 1.07 (m, 6H); MS (ESI(+)) m/e 390 (M+H)+.
Example 332
N- [4-( 1 -benzoyl- 1 ,2,3 ,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.39 (s, IH), 7.56-7.59 (m, 2H), 7.44- 7.49 (m, 5H), 7.34-7.40 (m, 4H), 7.29-7.34 (m, 2H), 5.91-6.27 (m, IH), 4.76-4.77 (bs, 4H), 4.02-4.26 (m, 2H), 3.36-3.59 (m, 2H), 2.51-2.61 (m, 2H); MS (ESI(+)) m/e 424 (M+H)+.
Example 333
N- { 4- [ 1 -(isopropylsulfonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro-2H- isoindole-2-carboxamide
The tide compound was prepared as described in Example 283, substituting propane- 2-sulfonyl chloride for methanesulfonyl chloride and N-[4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide for 5-amino-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.38-8.40 (m, IH), 7.56-7.59 (m, 2H), 7.29-7.38 (m, 6H), 6.11-6.14 (m, IH), 4.76-4.80 (m, 4H), 3.93-3.96 (m, 2H), 3.49 (t, 7 = 5.5 Hz, 2H), 3.35-3.45 (m, IH), 2.47-2.51 (m, 2H), 1.24 (d, J = 6.9 Hz, 6H); MS (ESI(-)) m/e 424 (M-H)\
Example 334
N-(r-isobutyryl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide
Example 334A
tert-butyl 4-(5-(isoindoline-2-carboxarnido)pyridin-2-yl)-5,6-dihydropyridine-l(2H)- carboxylate
The title compound was prepared as described in Example 280, substituting tert-butyl
4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate for lH-pyrazol-3-ylboronic acid and N-(6-chloropyridin-3-yl)isoindoline-2-carboxamide for 5- bromo-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide.
Example 334B
N-(6-(l,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl)isoindoline-2-carboxarnide
The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(5-(isoindoline-2-carboxarrddo)pyridin-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate.
Example 334C
tert-butyl 4-(5-(isoindoline-2-carboxarnido)pyridin-2-yl)-5,6-dihydropyridine-l(2H)- carboxylate
The title compound was prepared as described in Example 278, substituting isobutyryl chloride for acetyl chloride and N-(6-(l,2,3,6-tetrahydropyridin-4-yl)pyridin-3- yl)isoindoline-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ ppm 8.70 (d, J = 2.6 Hz, IH), 8.33-8.37 (m, IH), 7.95 (dd, J = 8.6, 2.6 Hz, IH), 7.44 (d, J = 8.6 Hz, IH), 7.28-7.36 (m, 4H), 6.54-6.56 (m, IH), 4.79 (s, 4H), 4.16-4.18 (m, 2H), 3.68 (t, 7 = 5.7 Hz, 2H), 2.86-2.97 (m, IH), 2.54-2.63 (m, 2H), 1.04 (d, 7 = 6.7 Hz, 6H); MS (ESI(-)) m/e 389 (M-H)\
Example 335
N-(r-benzoyl-1^2^3^6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide
The tide compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(6-(l,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl)isoindoline- 2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.71 (d, 7 = 2.5 Hz, IH), 8.61 (s, IH), 8.01 (dd, 7 = 8.6, 2.2 Hz, IH), 7.42-7.54 (m, 6H), 7.35-7.39 (m, 2H), 7.29-7.35 (m, 2H), 6.46-6.67 (m, IH),
4.79 (s, 4H), 4.05-4.32 (m, 2H), 3.77-3.94 (m, IH), 3.47-3.58 (m, IH), 2.61-2.65 (m, 2H); MS (ESI(+)) m/e 425 (M+H)+.
Example 336
N- [4-(4-benzoylpiperazin- 1 -yl)phenyl]- 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 336A
N-(4-(piperazin- 1 -yl)phenyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(isoindoline-2-carboxamido)phenyl)piperazine-l-carboxylate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxarrddo)benzamido)methyl)benzylcarbamate.
Example 336B
N- [4-(4-benzoylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(4-(piperazin-l-yl)phenyl)isoindoline-2-carboxamide for 5- amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.14 (s, IH), 7.38-7.50 (m, 7H), 7.28-7.38 (m, 4H), 6.87-6.91 (m, 2H), 4.74 (s, 4H), 3.39-3.90 (m, 4H), 3.01-3.17 (m, 4H); MS (ESI(+)) m/e 427 (M+H)+.
Example 337
N- { 4- [4-(isopropylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 283, substituting isopropylsulfonyl chloride for methanesulfonyl chloride and N-(4-(piperazin-l- yl)phenyl)isoindoline-2-carboxamide for 5-amino-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.16 (s, IH), 7.39-7.45 (m, 2H), 7.27-7.38 (m, 4H), 6.88-6.92 (m, 2H), 4.74 (s, 4H), 3.07-3.12 (m, 4H), 1.25 (d, 7 = 6.8 Hz, 6H); MS (ESI(+)) m/e 429 (M+H)+.
Example 338
N- { 4- [4-(phenylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole -2-carboxamide The title compound was prepared as described in Example 283, substituting benzenesulfonyl chloride for methanesulfonyl chloride and N-(4-(piperazin-l- yl)phenyl)isoindoline-2-carboxamide for 5-amino-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.14 (s, 1H), 7.65-7.80 (m, 5H), 7.35-7.41 (m, 2H), 7.27-7.37 (m, 4H), 6.81-6.85 (m, 2H), 4.72 (s, 4H), 3.09-3.15 (m, 4H), 2.99-3.04 (m, 4H); MS (ESI(-)) m/e 461 (M-H)\
Example 339
N- { 4-[3-(benzoylamino)pyrrolidin- 1 -yl]phenyl} - l,3-dihydro-2H-isoindole-2-carboxamide
Example 339A
tert-butyl l-(4-nitrophenyl)pyrrolidin-3-ylcarbamate
A solution of l-fluoro-4-nitrobenzene (508 mg, 3.6 mmol) and tert-butyl pyrrolidin-3- ylcarbamate (671 mg, 3.6 mmol) in N,N-dimethylformamide (7 mL) was heated at 55°C for 1.5 hours and then stirred overnight at room temperature. The reaction mixture was poured into water and the suspension was filtered with water washes to provide the title compound after drying.
Example 339B
tert-butyl 1 -(4-aminophenyl)pyrrolidin-3-ylcarbamate The title compound was prepared as described in Example 274, substituting (+/-)-tert- butyl l-(4-nitrophenyl)pyrrolidin-3-ylcarbamate for 5-nitro-N-[4-(propylcarbamoyl)phenyl]- 1 ,3-dihydro-2H-isoindole-2-carboxamide.
Example 339C
tert-butyl l-(4-(isoindoline-2-carboxamido)phenyl)pyrrolidin-3-ylcarbamate The title compound was prepared as described in Example 272, substituting (+/-)-tert- butyl l-(4-aminophenyl)pyrrolidin-3 -ylcarbamate for 4-arnino-N-propylbenzarnide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride in Example 272B.
Example 339D
N-[4-(3-aminopyrrolidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 2, substituting (+/-)-tert- butyl l-(4-(isoindoline-2-carboxarnido)phenyl)pyrrolidin-3 -ylcarbamate for tert-butyl 4-((4- (5-fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate in Example 2D.
Example 339E
N- { 4- [(3R)-3 -(benzoylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide and N- { 4- [(3S)-3-(benzoylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compounds were prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and (+/-)-N-(4-(3-arninopyrrolidin-l-yl)phenyl)isoindoline-2- carboxamide for 5-arrdno-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.61 (d, J = 6.8 Hz, IH), 8.01 (s, IH), 7.85-7.89 (m, 2H), 7.42-7.56 (m, 3H), 7.28-7.37 (m, 6H), 6.50 (d, 7 = 8.7 Hz, 2H), 4.72 (s, 4H), 4.56-4.67 (m, IH), 3.53-3.59 (m, IH), 3.36-3.45 (m, IH), 3.16-3.24 (m, IH), 2.22-2.31 (m, IH), 2.03-2.13 (m, IH); MS (ESI(+)) m/e 427 (M+H)+.
Example 340
N- { 4- [(3R)-3 -(butyrylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide and N- { 4-[(3S)-3-(butyrylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compounds were prepared as described in Example 278, substituting butyryl chloride for acetyl chloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.06 (d, J = 6.9 Hz, IH), 7.28-7.37 (m, 6H), 6.47 (d, 7 = 8.7 Hz, 2H), 4.72 (s, 4H), 4.36 (h, 7 = 5.7 Hz, IH), 3.41-3.47 (m, IH), 3.17-3.23 (m, IH), 2.89-3.05 (m, IH), 2.10-2.28 (m, IH), 2.05 (t, 7 = 7.3 Hz, 2H), 1.81-1.96 (m, IH), 1.45-1.58 (m, 2H), 0.85 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 393 (M+H)+.
Example 341
tert-butyl 4 - { 4 - [( 1 , 3 -dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } piperazine- 1 - carboxylate
Example 341 A
tert-butyl 4-(4-nitrophenyl)piperazine-l -carboxylate A solution of l-fluoro-4-nitrobenzene (500 mg, 3.54 mmol) and tert-butyl piperazine- 1 -carboxylate (726 mg, 3.9 mmol) in dimethylformamide was treated with potassium carbonate (735 mg, 5.32 mmol) and the suspension was heated at 55°C for 4 hours and then stirred overnight at room temperature. The reaction was poured into water and the suspension was filtered with water washes to provide the title compound after vacuum drying.
Example 34 IB
tert-butyl 4-(4-aminophenyl)piperazine-l -carboxylate
The title compound was prepared as described in Example 274, substituting tert-butyl 4-(4-nitrophenyl)piperazine-l -carboxylate for 5-nitro-N-[4-(propylcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide.
Example 341C
tert-butyl 4-(4-(isoindoline-2-carboxamido)phenyl)piperazine-l -carboxylate
The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(4-aminophenyl)piperazine-l -carboxylate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- d6) δ ppm 8.14 (s, IH), 7.38-7.44 (m, 2H), 7.27-7.39 (m, 4H), 6.88-6.90 (m, IH), 6.86 (s, IH), 4.73 (s, 4H), 3.40-3.51 (m, 4H), 2.98-3.02 (m, 4H), 1.42 (s, 9H); MS (ESI(-)) m/e 421 (M-H)\ Example 342
N-[4-(4-propionylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The tide compound was prepared as described in Example 278, substituting propionyl chloride for acetyl chloride and N-(4-(piperazin-l-yl)phenyl)isoindoline-2-carboxamide for 5- amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz,
DMSO- ) δ ppm 8.14 (s, IH), 7.38-7.44 (m, 2H), 7.28-7.39 (m, 4H), 6.87-6.90 (m, 2H), 4.74 (s, 4H), 3.54-3.60 (m, 4H), 2.95-3.10 (m, 4H), 2.36 (q, J = 7.4 Hz, 2H), 1.03 (s, IH), 1.00 (d, J = 7.4 Hz, 2H); MS (ESI(+)) m/e 379 (M+H)+.
Example 343
N-{4-[4-(cyclopropylcarbonyl)piperazin-l -yl]phenyl} -l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting cyclopropanecarbonyl chloride for acetyl chloride and N-(4-(piperazin- l- yl)phenyl)isoindoline-2-carboxamide for 5-amino-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.15 (s, IH), 7.38-7.45 (m, 2H), 7.28-7.39 (m, 4H), 6.87-6.93 (m, 2H), 4.74 (s, 4H), 3.73-3.90 (m, 2H), 3.50-3.70 (m, 2H), 3.02-3.18 (m, 4H), 1.98-2.07 (m, IH), 0.68-0.77 (m, 4H); MS (ESI(-)) m/e 389 (M-H)\
Example 344
N-(2-butyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2-carboxarnide
Example 344A
tert-butyl 5-(isoindoline-2-carboxamido)isoindoline-2-carboxylate In a 250 mL round bottom flask was mixed at room temperature triphosgene (234 mg, 0.790 mmol) in anhydrous dichloromethane (25 mL). To this solution was added dropwise over 15 minutes, a slurry of tert-butyl 5-aminoisoindoline-2-carboxylate (500 mg, 2.134 mmol) and diisopropylethylamine (0.410 ml, 2.347 mmol) in anhydrous dichloromethane (20 mL). The mixture was stirred overnight at room temperature. A solution of isoindoline (0.242 ml, 2.134 mmol) and diisopropylethylamine (0.410 ml, 2.347 mmol) in anhydrous dichloromethane (20 mL) was added in one portion. The reaction stirred overnight at room temperature. The solvent was removed and the residue was purified by normal phase flash chromatography to provide the title compound.
Example 344B
N-(isoindolin-5-yl)isoindoline-2-carboxamide
The title compound was prepared as described in Example 2D, substituting tert-butyl 5-(isoindoline-2-carboxamido)isoindoline-2-carboxylate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate. Example 344C
N-(2-butyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro
The title compound was prepared as described in Example 278, substituting butyryl chloride for acetyl chloride and N-(isoindolin-5-yl)isoindoline-2-carboxamide for 5-amino-N- (4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.39 (s, 1H), 7.59-7.61 (bs, 1H), 7.43-7.48 (m, 1H), 7.30-7.41 (m, 4H), 7.22 (t, 7 = 7.7 Hz, 1H), 4.77 (d, 7 = 13.9 Hz, 2H), 4.77 (s, 4H), 4.55-4.60 (m, 2H), 2.33 (td, 7 = 7.3, 3.7 Hz, 2H), 1.54-1.63 (m, 2H), 0.93 (td, 7 = 7.3, 1.4 Hz, 3H); MS (ESI(+)) m/e 350 (M+H)+.
Example 345
N-(2-isobutyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 278, substituting isobutyryl chloride for acetyl chloride and N-(isoindolin-5-yl)isoindoline-2-carboxamide for 5-arnino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.40 (s, 1H), 7.59-7.61 (bs, 1H), 7.46 (ddd, J = 10.8, 8.5, 2.1 Hz, 1H), 7.30- 7.38 (m, 4H), 7.20-7.24 (m, 1H), 4.82-4.87 (m, 2H), 4.76-4.77 (bs, 4H), 4.55-4.60 (m, 2H), 2.78 (h, 7 = 6.9 Hz, 1H), 1.07 (d, 7 = 6.7 Hz, 6H); MS (ESI(+)) m/e 350 (M+H)+.
Example 346
N-(2-benzoyl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2-carboxarnide The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(isoindolin-5-yl)isoindoline-2-carboxamide for 5-amino-N- (4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.40 (d, 7 = 8.8 Hz, 1H), 7.59-7.67 (m, 3H), 7.11-7.52 (m, 9H), 4.68-4.84 (m, 8H); MS (ESI(+)) m e 384 (M+H)+.
Example 347
N-[2-(3-methylbutyl)-2,3-dihydro-lH-isoindol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 429, substituting 3- methylbutanal for isobutyraldehyde and N-(isoindolin-5-yl)isoindoline-2-carboxamide for N- (4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)isoindoline-2-carboxarnide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.28 (s, 1H), 7.47 (s, 1H), 7.29-7.37 (m, 5H), 7.09 (d, 7 = 8.1 Hz, 1H), 4.75 (s, 4H), 3.77-3.79 (m, 2H), 3.74-3.76 (m, 2H), 2.64 (t, 7 = 7.5 Hz, 2H), 1.60-1.71 (m, 1H), 1.37-1.43 (m, 2H), 0.91 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 350 (M+H)+.
Example 348
N-[4-(hexyloxy)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1A, substituting 1-
(hexyloxy)-4-isocyanatobenzene for methyl 4-isocyanatobenzoate. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.17 (s, 1H), 7.39-7.45 (m, 2H), 7.27-7.39 (m, 4H), 6.81-6.85 (m, 2H), 4.74 (s, 4H), 3.91 (t, 7 = 6.5 Hz, 2H), 1.64-1.73 (m, 2H), 1.35-1.47 (m, 2H), 1.23-1.38 (m, 4H), 0.85-0.91 (m, 3H); MS (ESI(+)) m/e 339 (M+H)+.
Example 349
N- [4-( 1 -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-[4-(piperidin-4-yl)butyl]-l,3-dihydro-2H-isoindole-2- carboxamide for 5-arnino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 7.39 - 7.47 (m, 3 H) 7.22 - 7.40 (m, 6 H) 6.27 (t, 7=5.43 Hz, 1 H) 4.56 (s, 4 H) 4.36 - 4.52 (br s, 1 H) 3.52 (br s, 1 H) 3.00 - 3.15 (m, 2 H) 2.93 (br s, 1 H) 0.93 - 1.86 (series of br m, 12 H); MS (ESI(+)) m/e 406 (M+H)+.
Example 350
N-{4-[l-(pyridin-3-ylcarbonyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting nicotinoyl chloride hydrochloride for acetyl chloride and N-[4-(piperidin-4-yl)butyl]-l,3- dihydro-2H-isoindole-2-carboxamide for 5-amino-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.58 - 8.71 (m, 2 H) 7.87 (d, 7=7.5 Hz, 1 H) 7.52 (dd, 7=7.5, 4.8 Hz, 1 H) 7.22 - 7.36 (m, 4 H) 6.28 (br m, 1 H) 4.56 (s, 4 H) 4.44 (br m, 1 H) 3.38 - 3.57 (br m, 1 H) 2.95 - 3.15 (br m, 2 H) 2.68 - 2.84 (br m, 1 H) 0.95 - 1.84 (br series of m, 12 H); MS (ESI(+)) m/e 407 (M+H)+.
Example 351
N-[6-(4-chlorophenoxy)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 344A, substituting 6-(4- chlorophenoxy)hexan-l -amine for tert-butyl 5-aminoisoindoline-2-carboxylate. ¾ NMR (300 MHz, DMSO-d6) δ ppm 1.40 (q, 6 H), 1.70 (q, 2 H), 3.08 (q, 7=6.8 Hz, 2 H), 3.95 (t, 7=6.4 Hz, 2 H), 4.57 (s, 4 H), 6.27 (t, 7=5.4 Hz, 1 H), 6.85 - 7.01 (m, 2 H), 7.21 - 7.39 (m, 6 H); MS (ESI(+)) m/e 373 (M+H)+.
Example 352
N-[4-(piperidin-4-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide
Example 352A
tert-butyl 4-(4-(isoindoline-2-carboxamido)butyl)piperidine- 1 -carboxylate The title compound was prepared as described in Example 344, substituting tert-butyl 4-(4-aminobutyl)piperidine-l -carboxylate for tert-butyl 5-aminoisoindoline-2-carboxylate in Example 344A. Example 352B
N-[4-(piperidin-4-yl)butyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(isoindoline-2-carboxamido)butyl)piperidine-l-carboxylate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate. ¾ NMR (300 MHz, DMSO-d6) δ ppm 1.14 - 1.34 (m, 6 H), 1.35 - 1.57 (m, 3 H), 1.76 (d, 7=12.30 Hz, 2 H), 2.69 - 2.89 (m, 2 H), 3.07 (q, 7=6.74 Hz, 2 H), 3.21 (d, 7=12.70 Hz, 2 H), 4.57 (s, 4 H), 6.29 (t, 7=5.55 Hz, 1 H), 7.11 - 7.41 (m, 4 H), 8.31 (s, 1 H); MS (ESI(+)) m/e 299 (M+H)+.
Example 353
N,N'-hexane-l,6-diylbis(l,3-dihydro-2H-isoindole-2-carboxamide)
The title compound was prepared as described in Example 1A, substituting 1,6- diisocyanatohexane for methyl 4-isocyanatobenzoate. ¾ NMR (300 MHz, DMSO-d6) δ ppm 7.19 - 7.37 (m, 8 H) 6.28 (t, 7=5.59 Hz, 2 H) 4.57 (s, 8 H) 3.07 (q, 7=6.8 Hz, 4 H) 1.37 - 1.55 (m, 4 H) 1.21 - 1.37 (m, 4 H); MS (ESI(+)) m/e 407 (M+H)+.
Example 354
N-(4-phenylbutyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1A, substituting (4- isocyanatobutyl)benzene for methyl 4-isocyanatobenzoate. ¾ NMR (300 MHz, DMSO-iie) δ ppm 7.24-7.33 (m, 6H), 7.13-7.22 (m, 3H), 6.30 (t, 7 = 5.6 Hz, 1H), 4.56 (s, 4H), 3.06-3.13 (m, 2H), 2.59 (t, 7 = 7.4 Hz, 2H), 1.51-1.65 (m, 2H), 1.40-1.53 (m, 2H); MS (ESI(+)) m/e 295 (M+H)+.
Example 355
ethyl 6-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]hexanoate The title compound was prepared as described in Example 1A, substituting ethyl 6- isocyanatohexanoate for methyl 4-isocyanatobenzoate. ¾ NMR (300 MHz, DMSO-d6) δ ppm 7.25-7.33 (m, 4H), 6.29 (t, 7 = 5.6 Hz, 1H), 4.57 (s, 4H), 4.04 (q, 7 = 7.1 Hz, 2H), 3.02- 3.09 (m, 2H), 2.28 (t, 7 = 7.3 Hz, 2H), 1.48-1.60 (m, 2H), 1.39-1.50 (m, 2H), 1.23-1.34 (m, 2H), 1.16 (t, 7 = 7.1 Hz, 3H); MS (ESI(+)) m/e 305 (M+H)+.
Example 356
N-hexyl-l,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1A, substituting 1- isocyanatohexane for methyl 4-isocyanatobenzoate. ¾ NMR (300 MHz, DMSO-<i6) δ ppm 7.25-7.33 (m, 4H), 6.27 (t, 7 = 5.6 Hz, 1H), 4.57 (s, 4H), 3.02-3.10 (m, 2H), 1.36-1.51 (m, 2H), 1.25-1.30 (m, 6H), 0.81-0.92 (m, 3H); MS (ESI(-)) m/e 245 (M-H)\
Example 357
N-(3-phenylpropyl)-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1A, substituting (3- isocyanatopropyl)benzene for methyl 4-isocyanatobenzoate. ¾ NMR (300 MHz, DMSO-iie) δ ρριη 7.11-7.37 (m, 9H), 6.31 (t, 7 = 5.5 Hz, 1H), 4.57 (s, 4H), 3.07-3.14 (m, 2H), 2.60 (t, J = 7.6 Hz, 2H), 1.71-1.81 (m, 2H); MS (ESI(+)) m/e 281 (M+H)+.
Example 358
N-octyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1A, substituting 1- isocyanatooctane for methyl 4-isocyanatobenzoate. ¾ NMR (300 MHz, DMSO-iie) δ ppm 7.24-7.35 (m, 4H), 6.27 (t, J = 5.5 Hz, 1H), 4.57 (s, 4H), 3.02-3.09 (m, 2H), 1.40-1.47 (m, 2H), 1.25-1.27 (m, 10H), 0.81-0.89 (m, 3H); MS (ESI(+)) m/e 275 (M+H)+.
Example 359
N- { 6- [( 1 -methyl- 1 H-pyrazol-4-yl)amino] -6-oxohexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
Example 359A
6-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]hexanoic acid
The title compound was prepared as described in Example IB, substituting ethyl 6- [(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]hexanoate for methyl 4-(isoindoline-2- carboxamido)benzoate.
Example 359B
N- { 6- [( 1 -methyl- 1 H-pyrazol-4-yl)amino] -6-oxohexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting 1 -methyl - lH-pyrazol-4-amine for 3-phenylpropan-l -amine and 6-[(l,3-dihydro-2H-isoindol-2- ylcarbonyl)amino]hexanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.81 (s, 1H), 7.82 (s, 1H), 7.34-7.36 (m, 1H), 7.24-7.34 (m,
4H), 6.28 (t, J = 5.5 Hz, 1H), 4.56 (s, 4H), 3.75 (s, 3H), 3.03-3.10 (m, 2H), 2.22 (t, J = 7.3 Hz, 2H), 1.51-1.64 (m, 2H), 1.40-1.52 (m, 2H), 1.23-1.34 (m, 2H); MS (ESI(+)) m/e 356 (M+H)+.
Example 360
N- [6-(methylamino)-6-oxohexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting methylamine for 3-phenylpropan-l -amine and 6-[(l,3-dihydro-2H-isoindol-2- ylcarbonyl)amino]hexanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.60-7.72 (m, 1H), 7.25-7.33 (m, 4H), 6.24-6.29 (m, 1H), 4.57 (s, 4H), 2.94-3.09 (m, 2H), 2.54 (d, J = 4.6 Hz, 3H), 2.30 (t, J = 7.3 Hz, 1H), 2.04 (t, J = 7.4 Hz, 1H), 1.37-1.58 (m, 4H), 1.18-1.35 (m, 2H); MS (ESI(+)) m/e 290 (M+H)+. Example 361
N- { 6-0X0-6- [(3 -phenylpropyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 6-[(l,3- dihydro-2H-isoindol-2-ylcarbonyl)amino]hexanoic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.75-7.80 (m, 1H), 7.24- 7.34 (m, 6H), 7.12-7.22 (m, 3H), 6.27 (t, J = 5.5 Hz, 1H), 4.56 (s, 4H), 2.98-3.11 (m, 4H), 2.52-2.58 (m, 2H), 2.06 (t, J = 7.3 Hz, 2H), 1.62-1.72 (m, 2H), 1.37-1.58 (m, 4H), 1.12-1.33 (m, 2H); MS (ESI(+)) m/e 394 (M+H)+.
Example 362
N- { 6- [(3 -methylbutyl)amino] -6-oxohexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting 3- methylbutan-1 -amine for 3-phenylpropan-l -amine and 6-[(l,3-dihydro-2H-isoindol-2- ylcarbonyl)amino]hexanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.64-7.69 (m, 1H), 7.24-7.34 (m, 4H), 6.26 (t, J = 5.5 Hz, 1H), 4.57 (s, 4H), 2.99-3.10 (m, 4H), 2.03 (t, J = 7.3 Hz, 2H), 1.41-1.59 (m, 5H), 1.21-1.30 (m, 4H), 0.84 (d, J = 6.6 Hz, 6H); MS (ESI(+)) m/e 346 (M+H)+.
Example 363
N-{3-oxo-3-[(3-phenylpropyl)amino]propyl}-l,3-dihydro-2H-isoindole-2-carboxarnide
Example 363A
ethyl 3-(isoindoline-2-carboxamido)propanoate
The title compound was prepared as described in Example 1A, substituting ethyl 3- isocyanatopropanoate for methyl 4-isocyanatobenzoate.
Example 363B
3-(isoindoline-2-carboxamido)propanoic acid
The title compound was prepared as described in Example IB, substituting ethyl 3-
(isoindoline-2-carboxamido)propanoate for methyl 4-(isoindoline-2-carboxamido)benzoate.
Example 363C
N-{3-oxo-3-[(3-phenylpropyl)amino]propyl}-l,3-dihydro-2H-isoindole-2-carboxarnide The title compound was prepared as described in Example 1C, substituting 3- (isoindoline-2-carboxamido)propanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.87-7.92 (m, 1H), 7.22-7.32 (m, 6H), 7.12-7.19 (m, 3H), 6.36 (t, J = 5.5 Hz, 1H), 4.56 (s, 4H), 3.24-3.32 (m, 2H), 3.03-3.10 (m, 2H), 2.52-2.60 (m, 2H), 2.30 (t, J = 7.0 Hz, 2H), 1.63-1.74 (m, 2H); MS (ESI(+)) m/e 352 (M+H)+.
Example 364
N-{3-oxo-3-[4-(pyridin-2-yl)piperazin-l-yl]propyl}-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 1- (pyridin-2-yl)piperazine for 3-phenylpropan-l-amine and 3-(isoindoline-2- carboxamido)propanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.11 (ddd, 7 = 4.9, 2.0, 0.8 Hz, 1H), 7.53 (ddd, 7 = 8.7, 7.0, 1.9 Hz, 1H), 7.25-7.34 (m, 4H), 6.83 (d, 7 = 8.6 Hz, 1H), 6.65 (ddd, 7 = 7.1, 4.9, 0.8 Hz, 1H), 6.37 (t, 7 = 5.6 Hz, 1H), 4.57 (s, 4H), 3.44-3.61 (m, 8H), 3.28-3.37 (m, 2H), 2.54-2.61 (m, 2H); MS (ESI(+)) m/e 380 (M+H)+.
Example 365
N- { 3 - [(3-methylbutyl)amino] -3 -oxopropyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 1 3- methylbutan-1 -amine for 3-phenylpropan-l-amine and 3-(isoindoline-2- carboxamido)propanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ρριη 7.76-7.81 (m, 1H), 7.25-7.34 (m, 4H), 6.31-6.36 (m, 1H), 4.56 (s, 4H), 3.23-3.31 (m, 2H), 3.02-3.09 (m, 2H), 2.27 (t, 7 = 7.0 Hz, 2H), 1.46-1.62 (m, 1H), 1.27 (q, 7 = 7.1 Hz, 2H), 0.84 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 304 (M+H)+.
Example 366
N-[4-(l -propyl- lH-pyrazol-4-yl)benzyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 366A
N-(4-bromobenzyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 1A, substituting 1-bromo-
4-(isocyanatomethyl)benzene for methyl 4-isocyanatobenzoate.
Example 366B
N-[4-(l -propyl- lH-pyrazol-4-yl)benzyl]-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 1-propyl- 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid and N-(4-bromobenzyl)isoindoline-2-carboxamide for 5-bromo-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 0.85 (t, 7=7.5 Hz, 3 H), 1.70 - 1.92 (m, 2 H), 4.06 (t, 7=6.9 Hz, 2 H), 4.29 (d, 7=6.1 Hz, 2 H), 4.63 (s, 4 H), 6.91 (t, 7=5.9 Hz, 1 H), 7.18 - 7.40 (m, 6 H), 7.49 (d, 7=8.5 Hz, 2 H), 7.82 (s, 1 H), 8.12 (s, 1 H); MS (ESI(+)) m/e 361 (M+H)+.
Example 367
N- [4-( 1 -isobutyl- 1 H-pyrazol-4-yl)benzyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 1- isobutyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3- ylboronic acid and N-(4-bromobenzyl)isoindoline-2-carboxamide for 5-bromo-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ ppm 0.86 (d, 7=6.4 Hz, 6 H), 2.03 - 2.21 (m, 1 H), 3.91 (d, 7=7.1 Hz, 2 H), 4.28 (d, 7=5.9 Hz, 2 H), 4.63 (s, 4 H), 6.92 (t, 7=5.9 Hz, 1 H), 7.25 - 7.37 (m, 6 H), 7.50 (d, 7=8.3 Hz, 2 H), 7.83 (s, 1 H), 8.10 (s, 1 H); MS (ESI(+)) m/e 375 (M+H)+.
Example 368
N-(5- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl }pyridin-2-yl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting N-(2- pyridyl)piperazine for 3-phenylpropan-l -amine and 6-(isoindoline-2-carboxamido)nicotinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO-d6) δ ppm 9.21 (s, 1H), 8.39 (dd, J = 2.3, 0.8 Hz, 1H), 8.13 (dd, J = 4.9, 1.9 Hz, 1H), 8.00 (dd, J = 8.6, 0.8 Hz, 1H), 7.84 (dd, J = 8.6, 2.4 Hz, 1H), 7.56 (ddd, J = 8.7, 6.9, 1.9 Hz, 1H), 7.34-7.39 (m, 2H), 7.29-7.34 (m, 2H), 6.85 (d, J = 8.5 Hz, 1H), 6.67 (dd, J = 6.7, 4.9 Hz, 1H), 4.75-4.92 (bs, 4H), 3.47-3.81 (m, 8H); MS (ESI(+)) m/e 429 (M+H)+.
Example 369
N-{ 5-[(3-phenylpropyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 369A
methyl 6-(isoindoline-2-carboxamido)nicotinate The title compound was prepared as described in Example 344A, substituting methyl 6-aminonicotinate for tert-butyl 5-aminoisoindoline-2-carboxylate.
Example 369B
6-(isoindoline-2-carboxamido)nicotinic acid
The title compound was prepared as described in Example IB, substituting methyl 6- (isoindoline-2-carboxamido)nicotinate for methyl 4-(isoindoline-2-carboxamido)benzoate.
Example 369C
N- { 5-[(3-phenylpropyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 6- (isoindoline-2-carboxamido)nicotinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO-d6) δ ppm 9.25 (s, 1H), 8.74 (d, J = 2.4 Hz, 1H), 8.47-8.51 (m, 1H), 8.14 (dd, J = 8.8, 2.4 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.33-7.38 (m, 2H), 7.29-7.33 (m, 2H), 7.26-7.30 (m, 2H), 7.21-7.26 (m, 2H), 7.15-7.21 (m, 1H), 4.74-4.92 (bs, 4H), 3.25-3.32 (m, 2H), 2.64 (t, J = 7.6 Hz, 2H), 1.84 (p, J = 7.4 Hz, 2H); MS (ESI(+)) m/e 401 (M+H)+.
Example 370
N- { 5- [(3-methylbutyl)carbamoyl]pyridin-2-yl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 3- methylbutan- 1 -amine for 3-phenylpropan- 1 -amine and 6-(isoindoline-2- carboxamido)nicotinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. H NMR (400 MHz, DMSO-<¾) δ ppm 9.24 (s, IH), 8.73 (d, J = 2.4 Hz, IH), 8.42 (t, J = 5.5 Hz, IH), 8.13 (dd, J = 8.8, 2.4 Hz, IH), 7.99 (d, J = 8.7 Hz, IH), 7.25-7.37 (m, 4H), 4.71-4.95 (bs, 4H), 3.24-3.32 (m, 2H), 1.57-1.68 (m, IH), 1.43 (q, J = 7.1 Hz, 2H), 0.91 (d, J = 6.6 Hz, 6H); MS (ESI(+)) m/e 353 (M+H)+.
Example 371
N- { 5- [(3-phenylpropyl)carbamoyl] - 1 ,3-thiazol-2-yl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide
Example 371 A
methyl 2-(isoindoline-2-carboxamido)thiazole-5-carboxylate The title compound was prepared as described in Example 272B, substituting methyl
2-aminothiazole-5-carboxylate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride.
Example 37 IB
2-(isoindoline-2-carboxamido)thiazole-5-carboxylic acid The title compound was prepared as described in Example IB, substituting methyl 2-
(isoindoline-2-carboxamido)thiazole-5-carboxylate for methyl 4-(isoindoline-2- carboxamido)benzoate.
Example 371C
N- { 5- [(3-phenylpropyl)carbamoyl] - 1 ,3-thiazol-2-yl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting 2- (isoindoline-2-carboxamido)thiazole-5-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 11.00-11.19 (bs, IH), 8.34 (t, J = 5.6 Hz, IH), 7.98 (s, IH), 7.15-7.37 (m, 9H), 4.70-4.83 (m, 4H), 3.17-3.28 (m, 2H), 2.63 (t, 7 = 7.6 Hz, 2H), 1.81 (p, 7 = 7.4 Hz, 2H); MS (ESI(-)) m/e 405 (M-H)\
Example 372
N-{ 5-[(3-methylbutyl)carbamoyl]- 1 ,3-thiazol-2-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting 3- methylbutan-1 -amine for 3-phenylpropan-l -amine and 2-(isoindoline-2- carboxamido)thiazole-5-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 11.01-11.16 (bs, IH), 8.27 (t, 7 = 5.6 Hz, IH), 7.96 (s, IH), 7.29-7.36 (m, 4H), 4.73-4.88 (bs, 4H), 3.18-3.28 (m, 2H), 1.52-1.69 (m, IH), 1.34-1.44 (m, 2H), 0.90 (d, 7 = 6.6 Hz, 6H); MS (ESI(-)) m/e 357 (M-H)-.
Example 374
N-[4-(4-oxo-3,4-dmydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxarnide Example 374A
N-(4-(4,4,5,5-tetramethyl-1 ,2-dioxaborolan-2-yl)phenyl)isoindoline-2-carboxamide 500 mg (4-Isocyanatophenyl)boronic acid pinacolester (1.979 mmol) and 365 mg isoindoline (2.97 mmol) were dissolved in 10 ml dichloromethane and the resultant mixture was stirred over night at room temperature. After adding water, the mixture was extracted several times with dichloromethane, the combined organic phases were washed with dried over magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. Column chromatography of the residue with dichloromethane resulted in the title compound.
Example 374B
N-[4-(4-oxo-3,4-dmydrophthalazin-l-yl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxarnide 105 mg N-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)isoindoline-2- carboxamide (0.288 mmol) and 53 mg 4-chloro-l,2-dihydrophthalazin-l-one (0.288 mmol) were dissolved in 2.5 ml dioxane. Cesium carbonate (474 mg, 1.44 mmol) was dissolved in 0.25 ml water and the resulting solution added to the reaction mixture. After the addition of 27.8 mg [l,l'-bis(diphenylphosphino)-ferrocene]dichlorpalladium(II) (0.038 mmol) the reaction mixture was flushed with nitrogen and stirred for 30 minutes in the microwave (Biotage Initiator 2.5) at 110°C. Dioxane was removed under reduced pressure, water and dichloromethane added to the residue and the formed precipitation was filtered. After dissolving the solid matter in a larger amount of dichloromethane/methanol 8:2, silica gel was added and subsequently the solvent was removed under reduced pressure. This residue was was purified by column chromatography using dichloromethane/methanol 95:5. ¾ NMR (DMSO-d6 ,400MHz): δ ρριη 12.73 (s, 1 H), 8.55 (s, 1 H), 8.33 (dd, 1 H), 7.85-7.92 (m, 2 H), 7.73-7.78 (m, 3 H), 7.48 (d, 2 H), 7.35-7.38 (m, 2 H), 7.30-7.33 (m, 2 H), 4.81 (s, 4H). MS (ESI(-)) m/e 383.2 (M+H)+.
Example 375
N-[4-(isoquinolin-4-yl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxarnide
The title compound was prepared as described in Example 374B, substituting 4- chloro- 1,2-dihydrophthalazin-l -one with 4-bromoisoquinoline. ESI-MS [M+H+]= 366.1.
Example 376
N- [4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one. ESI-MS [M+H+]= 382.1.
Example 377
N-[4-(4-oxo-3,4,5,6,7,8-hexahydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide Example 377A
2-(4-Amino-benzoyl)-cyclohex- 1 -enecarboxylic acid To a suspension of 2.2 g magnesium turnings (83.5 mmol) in 15 ml tetrahydrofuran were added 0.1 mL 1,2-dibromethane to start the Grignard reaction followed by slow addition of 13.0 g 2-(4-bromphenyl)-l,l,l,3,3,3-hexamethyldisilazane (41 mmol) in 70 mL tetrahydrofuran over a period of 20 minutes at room temperature with subsequent stirring for further 30 minutes. The resulting mixture was added dropwise at -78°C to a solution of 4,5,6,7-tetrahydro-isobenzofuran-l,3-dione (5.6 g) in 70 mL tetrahydrofuran. The reaction mixture was slowly warmed to room temperature. Sulfuric acid (2 mL, 1 M) was added and the solvent was removed under reduced pressure. The residue was added carefully to 20 mL of 0.5 M sulfuric acid solution and the desired product started to precipitate and was extracted with ethyl acetate. Acidification of the water phase and extraction with ethyl acetate was continued until pH~4-5 (at least three times). The combined organic phases were washed with brine, dried over magnesium sulfate, filtered and the solvent was subsequently evaporated under reduced pressure. Purification of the raw material by column
chromatography with ethyl acetate /hexane 1 : 1 and subsequently 100% ethyl acetate resulted in the desired product.
Example 377B
4-(4-aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one 10.3 g of 2-(4-amino-benzoyl)-cyclohex-l -enecarboxylic acid (42 mmol) were dissolved in 45 mL ethanol, 2.7 g (54 mmol) hydrazine hydrate was added and the mixture was heated under reflux for 30 hours. Precipitation of the product already started several hours after heating. After cooling in the refrigerator overnight the precipitated product was filtered and washed with cold ethanol.
Example 377C
l,3-dihydro-isoindole-2-carboxylicacid [4-(4-oxo-3,4,5,6,7,8-hexahydro-phthalazin-l-yl)- phenyl] -amide
To a solution of 200 mg 4-(4-aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one (0.829 mmol) in 5 ml Ν,Ν-dimethylformamide were added 245 mg carbonic acid bis-(2,5- dioxo-pyrrolidin-l-yl) ester (0.912 mmol) and the reaction mixture was stirred overnight. 255 mg of isoindoline were added, the precipitation formed was dissolved by adding 0.8 ml N,N- dimethylformamide, and the reaction mixture was stirred overnight. Water was added, and the formed precipitation was washed with water/methanol and subsequently dried in vacuum to obtain the crude material. The crude material was refluxed in 20 ml ethanol for 2 hours, cooled to room temperature, filtered and dried to obtain the desired product. ESI-MS
[M+H+]= 387.2. Example 378
N-[4-(8-fluoro-4-oxo-3,4-dihydrophmalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-5-fluoro-2H- phthalazin-l-one. ESI-MS [M+H+]= 401.1.
Example 379
5-fluoro-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with 5-fluoro-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 401.1.
Example 380
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]-5-(pyrrolidin- 1 -ylmethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with 5-pyrrolidin-l-ylmethyl-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 466.2.
Example 381
5-(morpholin-4-ylmethyl)-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with 5-morpholin-4-ylmethyl-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 481.3.
Example 382
5-methoxy-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with 5-methoxy-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 412.2.
Example 383
5-[(4-methylpiperazin- 1 -yl)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with 5-(4-methyl-piperazin-l-ylmethyl)-2,3-dihydro-lH- isoindole. ESI-MS [M+H+]= 495.2.
Example 384
5-cyano-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with 2, 3-dihydro-lH-isoindole-5-carbonitrile. ESI-MS [M+H+]= 407.1.
Example 385
5-chloro-N-[4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with 5-chloro-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 416.1.
Example 386
N-[4-(4-oxo-4,5-dihydro-3H-2,3-benzodiazepin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with l-(4-amino-phenyl)-3,5-dihydro- benzo[d][l,2]diazepin-4-one. ESI-MS [M+H+]= 397.2.
Example 387
N-[4-(l -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] -5-(pyrrolidin- 1 -ylmethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with 5-pyrrolidin-l-ylmethyl-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 465.2.
Example 388
N- { 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-5- trifluoromethyl-2H-phthalazin-l-one. ESI-MS [M+H+]= 451.1. Example 389
5 - [(dimethylamino)methyl] -N-[4-(l-oxo-l,2 -dihydroisoquinolin-4 -yl)phenyl] -1,3 -dihydro -
2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with (2,3-dihydro-lH-isoindol-5-ylmethyl)-dimethyl-amine. ESI- MS [M+H+]= 439.3.
Example 390
5- [(diethylamino)methyl] -N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with (2,3-dihydro-lH-isoindol-5-ylmethyl)-diethyl-amine. ESI- MS [M+H+]= 467.3.
Example 391
5-[(4-methylpiperazin- 1 -yl)methyl]-N-[4-(l -oxo- 1 ,2 -dihydroisoquinolin-4 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-aminophenyl)isoquinolin- l(2H)-one and isoindoline with 5-(4-methyl-piperazin-l-ylmethyl)-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 494.3.
Example 392
5-[(dimethylamino)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with (2,3-dihydro-lH-isoindol-5-ylmethyl)-dimethyl-amine. ESI-MS [M+H+]= 440.2.
Example 393
5-[(diethylamino)methyl] -N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro -2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with (2,3-dihydro-lH-isoindol-5-ylmethyl)-diethyl-amine. ESI-MS [M+H+]= 468.2. Example 394
N- { 4- [4-0X0-8 -(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } -5 -(pyrrolidin- 1 - ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide The tide compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-5- trifluoromethyl-2H-phthalazin-l-one and isoindoline with 5-pyrrolidin-l-ylmethyl-2,3- dihydro-lH-isoindole. ESI-MS [M+H+]= 534.2.
Example 395
5-[( 1 -methylpiperidin-4-yl)oxy]-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with 5-(l-methyl-piperidin-4-yloxy)-2,3-dihydro-lH- isoindole. ESI-MS [M+H+]= 496.2.
Example 396
5 - { [(3R)-3-fluoropyrrolidin- 1 -yl] methyl } -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with 5-((R)-3-fluoro-pyrrolidin-l-ylmethyl)-2,3-dihydro- lH-isoindole. ESI-MS [M+H+]= 484.2.
Example 397
5-{ [(3S)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]- l,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with 5-((S)-3-fluoro-pyrrolidin-l-ylmethyl)-2,3-dihydro-lH- isoindole. ESI-MS [M+H+]= 484.2.
Example 398
5-(azetidin- 1 -ylmethyl)-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]- 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2H- phthalazin-l-one and isoindoline with 5-azetidin-l-ylmethyl-2,3-dihydro-lH-isoindole. ESI- MS [M+H+]= 452.2. Example 399
N-[4-(l -oxo-1, 2-dihydropyrrolo[l,2-d] [1,2,4] triazin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-
2-carboxamide
Example 399A
N'-(4-bromobenzoyl)-lH-pyrrole-2-carbohydrazide
To 0.750 g of lH-pyrrole-2-carbohydrazide (5.99 mmol) in 50 ml tetrahydrofuran was added 1.315 g 4-bromobenzoyl chloride (5.99 mmol) and 1 ml pyridine (11.99 mmol) at room temperature under nitrogen. After one hour of stirring at room temperature, the desired product precipitated. The precipitate was filtered, washed with minimum dichloromethane and methanol and dried to afford the title compound. ¾ NMR (400 MHz, DMSO-d6) δ 11.63 (s, 1H), 10.47 (s, 1H), 10.04 (s, 1H), 7.84 - 7.88 (m, 2H), 7.75 (d, J = 8.8, 1H), 7.75 (q, J = 4.2, 1H), 6.91-6.95 (m, 2H), 6.33-6.15 (m, 1H).
Example 399B
2-(4-bromophenyl)-5-(lH-pyrrol-2-yl)-l,3,4-oxadiazole To 1.2 g of N'-(4-bromobenzoyl)-lH-pyrrole-2-carbohydrazide (3.89 mmol) was added 5 ml phosphoryl trichloride (1.65 mmol). The reaction was stirred for 25 minutes at 120°C. The reaction was cooled to 0°C, and ice was added. The resulting solid was filtered, and washed with water, NH4OH, dichloromethane and ethyl acetate. Purification by silica gel chromatography (dichloromethane : methanol = 9 : 1) resulted in the desired product. ¾ NMR (400 MHz, DMSO-d6) δ 12.32 (s, 1H), 8.05 - 8.00 (m, 2H), 7.89 - 7.83 (m, 2H), 7.18 (td, J = 1.5, 2.6, 1H), 6.97 (ddd, J = 1.5, 2.4, 3.7, 1H), 6.33 (dt, J = 2.4, 3.6, 1H). 13C NMR (400 MHz, DMSO-d6) δ 110.16, 112.49, 115.12, 122.71, 123.96, 125.23, 128.26, 132.49, 159.37, 161.57.
Example 399C
4-(4-bromophenyl)pyrrolo[l,2-d] [l,2,4]triazin-l(2H)-one
To 0.469 g sodium ethanolate (6.89 mmol) dissolved in 20 ml ethanol was added 1.0 g 2-(4-bromophenyl)-5-(lH-pyrrol-2-yl)-l,3,4-oxadiazole (3.45 mmol) at room temperature under nitrogen and the mixture was stirred at room temperature for 5 minutes. The reaction was heated at 160°C for 2 hours in a microwave (Biotage Initiator 2.5). The reaction was monitored by TLC dichloromethane/methanol = 9/1. Additional equivalents of sodium ethanolate were added and additional heating was carried out until completion of the reaction according to TLC. The reaction mixture was concentrated under reduced pressure and adsorbed on silica gel. The product was purified by silica gel chromatography (gradient: cyclohexane/ethylacetate = 0 - 100%) to afford the title compound. ¾ NMR (400 MHz, DMSO-d6) δ 12.09 (s, 1H), 7.85 - 7.78 (m, 2H), 7.76 - 7.69 (m, 2H), 7.39 (dd, J = 1.3, 2.9, 1H), 7.16 (dd, J = 1.4, 3.8, 1H), 6.77 (dd, J = 2.9, 3.8, 1H). 13C NMR (400 MHz, DMSO-d6) δ 154.22, 136.46, 131.98, 130.90, 129.52, 124.07, 124.00, 118.80, 114.42, 111.01. Example 399D
4-(4-aminophenyl)pyrrolo[l,2-d] [l,2,4]triazin-l(2H)-one To 1.181 g 4-(4-bromophenyl)pyrrolo[l,2-d][l,2,4]triazin-l(2H)-one (4.07 mmol) in toluene (10 ml) was added 0.080 g 2-dicyclohexylphosphino-2'-(N,N- dimethylamino)biphenyl (0.2004 mmol), 0.063 g tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (0.061 mmol) and 10.58 ml lithium bis(trimethylsilyl)amide 1M in toluene (10.58 mmol) under nitrogen at room temperature and the reaction was subsequently heated at 150°C for 5 minutes by microwave (Biotage Initiator 2.5). Thin layer chromotography in cyclohexane/ ethyl acetate = 1/ 1 showed no starting material. After cooling the reaction mixture, 7 ml of 2N aqueous HC1 was added, the mixture stirred for 30 minutes, and the mixture was basified until pH = 10 by addition of aqueous NaOH (2N). A precipitate was formed. The solid was filtered and washed with ether and dried overnight to obtain the title compound. LCMS: m/z 227.0 (M+H). The filtrate was extracted with ethyl acetate. The organic phase was combined with the ether from the washing, dried over Na2S04, filtered, and the solvent was evaporated under reduced pressure. The raw material was adsorbed on silica (dissolved in ethyl acetate), then purified by silica gel chromatography (cyclohexane : ethyl acetate gradient, the product was eluted at 80% of ethyl acetate) to afford additional title compound. ¾ NMR (400 MHz, DMSO-d6) δ 11.85 (br. s., 1 H), 7.32 - 7.44 (m, 3 H), 7.09 (dd, J=3.8, 1.3 Hz, 1H), 6.66 - 6.77 (m, 3 H), 5.67 (s, 2 H). 13C NMR (400 MHz, DMSO-d6) δ 154.15, 150.86, 137.98, 129.55, 123.98, 118.70, 116.65, 113.95, 113.32, 110.58.
Example 399E
[4-(l-Oxo-l,2-dmydro-pyrrolo[l,2-d] [l,2,4]triazin-4-yl)-phenyl]-carbarnic acid phenyl ester
To a suspension of 50 mg 4-(4-aminophenyl)pyrrolo[l,2-d][l,2,4]triazin-l(2H)-one (0.22 mmol) in 1 ml tetrahydrofuran at room temperature a solution of 0.03 ml pyridine (0.3 mmol) in 0.5 ml of tetrahydrofuran was added over 5 minutes. Subsequently, 0.03 ml phenylchlorformate (0.23 mmol) dissolved in 3 ml of tetrahydrofuran was added over 30 minutes and the reaction was stirred at room temperature overnight. The solvent was evaporated on vacuo and the mixture was directly incorporated on silica by dichloromethane. The mixture was purified by silica gel chromatography (4 g, cyclohexane :ethylacetate gradient) to afford crude material which was purified by column chromatography
(cyclohexane :ethylacetate gradient) to afford the title compound.
Example 399F
N-[4-(l -oxo-1, 2-dihydropyrrolo[l,2-d] [1,2,4] triazin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-
2-carboxamide
40 mg [4-(l-Oxo-l,2-dihydro-pyrrolo[l,2-d][l,2,4]triazin-4-yl)-phenyl]-carbarnic acid phenyl ester (0.115mmol) were dissolved in 0.3 ml DMSO. A mixture of 15 mg isoindoline (0.121mmol) in 0.2 ml DMSO was added at room temperature and the reaction was stirred at room temperature over night. The reaction mixture was diluted in ethyl acetate and washed with water, aqueous HC1, water, aqueous NaOH, and water. The solvent was evaporated under reduced pressure to afford the title compound.
Example 400
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-l-ylmethyl)- l,3-dihydro-2H-isoindole-2-carboxamide
Example 400A
5-pyrrolidin-l-ylmethyl-l,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester To a solution of 1.25 g 5-hydroxymethyl-l,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (5.01 mmol) in 14 ml dichloromethane was slowly added 0.781 ml methanesulfonyl chloride (10.03 mmol) at room temperature. Subsequently the mixture was heated for 4 hours at reflux. LCMS control indicted a near complete formation of the corresponding mesylate, which was not isolated. After cooling to room temperature, 1.244 ml pyrrolidine (15.04 mmol) were added and the mixture was stirred at room temperature overnight. The reaction was complete according to LCMS. Water was added to the reaction mixture, the acidic aqueous phase was extracted two times with dichloromethane, and the water phase was basified and extracted three times with ethyl acetate. The combined ethyl acetate solutions were extracted with brine, dried over Na2S04, filtered, and the organic solvent was removed under reduced pressure to provide the title compound. The
dichloromethane phase was extracted two times with diluted NaOH, once with brine and then dried over Na2S04. Filtration and removal of the organic solvent under reduced pressure provided additional title compound. Both fractions were combined and used in the next step without further purification. LCMS: m/z 303.2 (M+H).
Example 400B
5-pyrrolidin- 1 -ylmethyl-2,3-dihydro- lH-isoindole
To a solution of 1.90 g 5-pyrrolidin-l-ylmethyl-l,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (raw material; 4.96 mmol) in 5 ml dichloromethane was added 3.82 ml trifluoroacetic acid (49.6 mmol) and the reaction mixture was stirred at room temperature overnight. The trifluoroacetic acid and dichloromethane were evaporated under reduced pressure, water was added to the residue, the acidic aqueous phase extracted two times with ethyl acetate, the aqueous phase was basified with diluted NaOH and then subsequently extracted three times with dichloromethane. The dichloromethane phase was washed once with brine, dried over Na2S04, filtered, and the solvent was removed under vacuum. The title compound was used without further purification in the next step. LCMS: m/z 203.2 (M+H).
Example 400C
5-pyrrolidin- 1 -ylmethyl- 1 ,3-dihydro-isoindole-2-carboxylic acid [4-(l -oxo- 1 ,2-dihydro- pyrrolo[ 1 ,2-d] [ 1 ,2,4] triazin-4-yl)-phenyl] -amide The title compound was prepared as described in Example 399E and Example 399F, substituting isoindoline with 5-pyrrolidin-l-ylmethyl-2,3-dihydro-lH-isoindole. LCMS: m/z 455.2 (M+H).
Example 401
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperidine- 1 - carboxylate
The title compound was prepared as described in Example 272A, substituting tert- butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6-dihydropyridine- 1(2H) -carboxylate for 4-nitro-N-propylbenzamide. ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.26 (s, 1H), 7.46-7.48 (m, 2H), 7.34-7.39 (m, 2H), 7.28-7.33 (m, 2H), 7.10-7.13 (m, 2H), 4.75 (s, 4H), 4.02-4.08 (m, 2H), 2.71-2.90 (m, 2H), 2.57-2.68 (m, 1H), 1.71-1.76 (m, 2H), 1.40-1.51 (m, 2H), 1.42 (s, 9H); MS (ESI(-)) m/e 420 (M-H)\
Example 402
N-[4-(5-propyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxarnide
Example 402 A
N-(4-cyanophenyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 1A, substituting 4- isocyanatobenzonitrile for methyl 4-isocyanatobenzoate.
Example 402B
(Z)-N-(4-(N'-hydroxycarbarnimidoyl)phenyl)isoindoline-2-carboxarnide
In a 25 mL pressure tube were mixed N-(4-cyanophenyl)isoindoline-2-carboxamide (500 mg, 1.899 mmol), hydroxylamine hydrochloride (264 mg, 3.80 mmol), and triethylamine (1.323 ml, 9.50 mmol) in ethanol (6 ml)/water (0.5 ml). The reaction vessel was sealed and heated at 80 °C for four hours. The reaction mixture was diluted with water and the solid was filtered off with water washes. HPLC purification provided the title compound.
Example 402C
N-[4-(5-propyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxarnide In a 4 mL vial was mixed (Z)-N-(4-(N'-hydroxycarbamimidoyl)phenyl)isoindoline-2- carboxamide (50 mg, 0.169 mmol), butyric acid (0.017 ml, 0.186 mmol), 1- hydroxybenzotriazole hydrate (12.92 mg, 0.084 mmol), and N-methylmorpholine (0.056 ml, 0.506 mmol) in anhydrous dimethylformamide (2 ml). To this solution was added N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (48.5 mg, 0.253 mmol) and the mixture was stirred overnight at ambient temperature. The solution was diluted with ethyl acetate and washed with water, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried with sodium sulfate, decanted, and concentrated. The residue was taken up in anhydrous toluene (1 ml), and the mixture was heated at 110 °C for 2 days. The reaction was diluted with water; and the solids that formed were filtered and washed with water and ether to provide the title compound. ¾ NMR (500 MHz, DMSO- ) δ ppm 8.68 (s, IH), 7.89-7.91 (m, 2H), 7.78-7.80 (m, 2H), 7.36-7.40 (m, 2H), 7.30-7.34 (m, 2H), 4.76-4.85 (m, 4H), 2.96 (t, 7 = 7.4 Hz, 2H), 1.81 (hex, 7 = 7.4 Hz, 2H), 0.99 (t, 7 = 7.4 Hz, 3H); MS (ESI(-)) m/e347 (M- H)\
Example 403
N-[4-(piperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-{4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl}piperidine-l-carboxylate for tert- butyl 4-((4-(5-fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate. ¾ NMR (500 MHz, DMSO- ) δ ppm 8.28 (s, IH), 7.46-7.48 (m, 2H), 7.34-7.37 (m, 2H), 7.30- 7.33 (m, 2H), 7.09-7.12 (m, 2H), 4.75-4.76 (bs, 4H), 3.09-3.17 (m, 2H), 2.68 (td, 7 = 12.3, 2.6 Hz, 2H), 2.57 (tt, 7 = 12.0, 3.4 Hz, IH), 1.71-1.75 (m, 2H), 1.56 (qd, 7 = 12.5, 3.9 Hz, 2H); MS (ESI(+)) m/e 322 (M+H)+.
Example 404
N-{5-[((3R)-tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-2-yl}-l,3-dihydro-2H- isoindole-2-carboxamide and N-{5-[((3S)-tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-2- yl}-l,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting
(tetrahydrofuran-3-yl)methanamine for 3-phenylpropan-l -amine and 6-(isoindoline-2- carboxamido)nicotinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. H NMR (400
MHz, DMSO- ) δ ppm 9.26 (s, IH), 8.74 (d, 7 = 2.4 Hz, IH), 8.56-8.60 (m, IH), 8.14 (dd, 7 = 8.8, 2.5 Hz, IH), 8.00 (d, 7 = 8.8 Hz, IH), 7.26-7.40 (m, 4H), 4.59-5.02 (m, 4H), 3.75 (td, 7 = 8.0, 5.7 Hz, IH), 3.69 (dd, 7 = 8.5, 6.9 Hz, IH), 3.59-3.66 (m, IH), 3.48 (dd, 7 = 8.5, 5.2 Hz, IH), 3.18-3.31 (m, 2H), 2.43-2.51 (m, IH), 1.90-1.99 (m, IH), 1.56-1.65 (m, IH); MS (ESI(-)) m/e 365 (M-H)\
Example 405
N- [4-( 1 -butyrylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 278, substituting butyryl chloride for acetyl chloride and N-[4-(piperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide for 5-arrdno-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾
NMR (400 MHz, DMSO- ) δ ppm 8.27 (s, IH), 7.46-7.49 (m, 2H), 7.34-7.39 (m, 2H), 7.28- 7.33 (m, 2H), 7.11-7.14 (m, 2H), 4.75-4.76 (bs, 4H), 4.52-4.57 (m, IH), 3.94-4.00 (m, IH), 3.03-3.11 (m, IH), 2.64-2.75 (m, IH), 2.51-2.63 (m, IH), 2.31 (t, 7 = 7.4 Hz, 2H), 1.73-1.81 (m, 2H), 1.47-1.59 (m, 3H), 1.32-1.47 (m, IH), 0.85-0.95 (m, 3H); MS (ESI(+)) m/e 392 (M+H)+. Example 406
N- [4-( 1 -isobutyrylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The tide compound was prepared as described in Example 278, substituting isobutyryl chloride for acetyl chloride and N-[4-(piperidin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (500 MHz, DMSO- ) δ ppm 8.28 (s, IH), 7.46-7.48 (m, 2H), 7.34- 7.39 (m, 2H), 7.29-7.33 (m, 2H), 7.12-7.14 (m, 2H), 4.75-4.76 (bs, 4H), 4.53-4.58 (m, IH), 4.03-4.07 (m, IH), 3.06-3.14 (m, IH), 2.86-2.93 (m, IH), 2.67-2.74 (m, IH), 2.53-2.61 (m, IH), 1.75-1.84 (m, 2H), 1.45-1.56 (m, IH), 1.33-1.45 (m, IH), 1.03 (d, J = 6.7 Hz, 3H), 1.00 (d, J = 6.6 Hz, 3H); MS (ESI(-)) m/e 390 (M-H)\
Example 407
N-[4-( 1 -benzoylpiperidin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-[4-(piperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide for 5-arnino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾
NMR (500 MHz, DMSO- ) δ ppm 8.29 (s, IH), 7.47-7.50 (m, 2H), 7.41-7.47 (m, 5H), 7.34- 7.38 (m, 2H), 7.29-7.33 (m, 2H), 7.16-7.18 (m, 2H), 4.75-4.76 (bs, 4H), 4.54-4.64 (m, IH), 3.57-3.74 (m, IH), 3.02-3.21 (m, IH), 2.79-2.93 (m, IH), 2.75 (tt, J = 11.9, 3.4 Hz, IH), 1.68- 1.88 (m, 2H), 1.54-1.63 (m, 2H); MS (ESI(-)) m/e 424 (M-H)\
Example 408
N-{4-[5-(3-methylbutyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 402C, substituting 4- methylpentanoic acid for butyric acid. :H NMR (500 MHz, DMSO- ) δ ppm 8.69 (s, IH), 7.89-7.91 (m, 2H), 7.77-7.79 (m, 2H), 7.36-7.39 (m, 2H), 7.31-7.34 (m, 2H), 4.80-4.81 (bs, 4H), 2.96-3.00 (m, 2H), 1.66-1.72 (m, 2H), 1.59-1.67 (m, IH), 0.93 (d, J = 6.4 Hz, 6H); MS (ESI(-)) m/e 375 (M-H)\
Example 409
N-[4-(5-benzyl- 1 ,2,4-oxadiazol-3-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 402C, substituting phenylacetic acid for butyric acid. ¾ NMR (500 MHz, DMSO- ) δ ppm 8.69 (s, IH), 7.87- 7.90 (m, 2H), 7.77-7.79 (m, 2H), 7.35-7.42 (m, 6H), 7.29-7.34 (m, 3H), 4.75-4.84 (m, 4H), 4.42 (s, 2H); MS (ESI(+)) m/e 397 (M+H)+.
Example 410
N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide A racemic mixture of N-(4-{ [tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide (250 mg) was dissolved in methanol and separated using SCF-LC with a ChiralPak AD-H 21x250mm column to provide N-(4-{ [(3S)- tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 -dmydro-2H-isoindole-2-carboxarnide. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.58 (s, IH), 8.38 (t, J = 5.7 Hz, IH), 7.75-7.79 (m, 2H), 7.64-7.69 (m, 2H), 7.30-7.41 (m, 4H), 4.78-4.79 (bs, 4H), 3.57-3.78 (m, 3H), 3.48 (dd, J = 8.5, 5.2 Hz, IH), 3.17-3.28 (m, 2H), 2.41-2.50 (m, IH), 1.87-2.04 (m, IH), 1.54-1.66 (m, IH); MS (ESI(+)) m/e 366 (M+H)+.
Example 411
N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide
A racemic mixture of N-(4-{ [tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide (250 mg) was dissolved in methanol and separated using SCF-LC with a ChiralPak AD-H 21x250mm column to provide N-(4-{ [(3R)- tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.57 (s, IH), 8.38 (t, J = 5.7 Hz, IH), 7.75-7.79 (m, 2H), 7.64-7.69 (m, 2H), 7.30-7.39 (m, 4H), 4.78-4.79 (bs, 4H), 3.57-3.78 (m, 3H), 3.48 (dd, 7 = 8.5, 5.3 Hz, IH), 3.13-3.29 (m, 2H), 2.40-2.50 (m, IH), 1.87-2.07 (m, IH), 1.54-1.66 (m, IH); MS (ESI(+)) m/e 366 (M+H)+.
Example 422
tert-butyl 4-{6-[(l,3-dmydro-2H-isoindol-2-ylcarbonyl)arnino]-lH-benzimidazol-2- yl } piperazine- 1 -carboxylate
Example 422A
tert-butyl 4-(5-nitro-lH-benzo[d]imidazol-2-yl)piperazine-l -carboxylate
In a 20 mL sealed tube under nitrogen, a mixture of tert-butyl piperazine- 1- carboxylate (0.943 g, 5.06 mmol), 2-chloro-5-nitro-lH-benzo[d]imidazole (0.5 g, 2.53 mmol) and ethanol (9.5 mL) was heated at 135°C for 2 hours. The reaction was concentrated and the residue was purified by reverse-phase chromatography to provide the title compound.
Example 422B
tert-butyl 4-(5-arnino-lH-benzo[d]imidazol-2-yl)piperazine-l -carboxylate
The title compound was prepared as described in Example 274, substituting tert-butyl 4-(5-nitro-lH-benzo[d]imidazol-2-yl)piperazine-l -carboxylate for 5-nitro-N-[4- (propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide.
Example 422C
tert-butyl 4-{6-[(l,3-dmydro-2H-isoindol-2-ylcarbonyl)arnino]-lH-benzimidazol-2- yl } piperazine- 1 -carboxylate The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(5-arnino-lH-benzo[d]imidazol-2-yl)piperazine-l-carboxylate for 4-amino-N- propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ ppm 10.90-11.08 (bs, IH), 7.84-7.85 (m, IH), 7.46-7.48 (m, IH), 7.27-7.35 (m, 4H), 7.04-7.06 (m, 2H), 4.76 (s, 4H), 3.46 (s, 8H), 1.44 (s, 9H); MS (ESI(+)) m/e 463 (M+H)+.
Example 423
N-[2-(piperazin-l-yl)-lH-benzirnidazol-6-yl]-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-{6-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)arnino]-lH-benzimidazol-2-yl}piperazine-l- carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate. ¾ NMR (300 MHz, DMSO-iie) δ ppm 11.04-11.29 (m, IH), 8.08-8.12 (bs, IH), 7.41-7.58 (m, IH), 7.24-7.39 (m, 4H), 7.04-7.06 (m, 2H), 4.76 (s, 4H), 3.37-3.44 (m, 4H), 2.85-2.89 (m, 4H); MS (ESI(+)) m/e 363 (M+H)+.
Example 424
N-[4-(propylcarbamoyl)phenyl]-5-vinyl-l,3-dmydro-2H-isoindole-2-carboxarnide In a sealed vial under nitrogen, a mixture of potassium vinyltrifluoroborate (100 mg, 0.75 mmol), 5-bromo-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide (150 mg, 0.37 mmol), bis(ttiphenylphosphine)palladium(II) chloride and saturated aqueous sodium bicarbonate (0.62 ml) in dimethylformamide was heated at 85°C for 5 hours. The reaction was poured into water, filtered, dried and purified by reverse-phase chromatography to provide the title compound. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.57 (s, IH), 8.25 (t, J = 5.7 Hz, IH), 7.75-7.78 (m, 2H), 7.63-7.67 (m, 2H), 7.47 (s, IH), 7.42 (dd, 7 = 7.9, 1.5 Hz, IH), 7.34 (d, 7 = 7.8 Hz, IH), 6.77 (dd, 7 = 17.6, 10.9 Hz, IH), 5.85 (dd, 7 = 17.6, 1.0 Hz, IH), 5.27 (d, 7 = 11.0 Hz, IH), 4.77-4.78 (bs, 4H), 3.16-3.22 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 350 (M+H)+.
Example 428
N-{4-[5-(tetrahydrofuran-3-yl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 402C, substituting tetrahydrofuran-3-carboxylic acid for butyric acid. ¾ NMR (500 MHz, DMSO-d6) δ ppm 8.69 (s, IH), 7.89-7.92 (m, 2H), 7.78-7.81 (m, 2H), 7.36-7.40 (m, 2H), 7.30-7.34 (m, 2H), 4.80-4.81 (bs, 4H), 4.08 (dd, 7 = 8.6, 7.6 Hz, IH), 3.97 (dd, 7 = 8.6, 5.4 Hz, IH), 3.86-3.95 (m, 2H), 3.79-3.85 (m, IH), 2.40 (dddd, 7 = 12.5, 9.0, 7.6, 5.9 Hz, IH), 2.26 (ddt, 7 = 7.7, 12.4, 6.2 Hz, IH); MS (ESI(-)) m/e 375 (M-H)\ Example 429
N- [4-( 1 -isobutyl- 1 ,2,3 ,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide
In a 4 mL were mixed N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)isoindoline-2- carboxamide (50 mg, 0.157 mmol) and isobutyraldehyde (0.014 ml, 0.157 mmol) in anhydrous dichloroethane (2 ml) at room temperature. Sodium triacetoxyborohydride (46.4 mg, 0.219 mmol) was added, and reaction was stirred overnight. The reaction mixture was diluted with water, ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated and the organic layer was washed with brine. The organic layer was diluted with methanol, dried with sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography to provide the title compound. ¾ NMR (400 MHz, DMSO-d6) δ ppm
8.35 (s, IH), 7.53-7.55 (m, 2H), 7.30-7.38 (m, 6H), 6.06-6.08 (m, IH), 4.77 (s, 4H), 3.01-3.03 (m, 2H), 2.57 (t, 7 = 5.6 Hz, 2H), 2.41-2.47 (m, 2H), 2.14 (d, J = 7.3 Hz, 2H), 1.77-1.88 (m, IH), 0.88 (d, J = 6.5 Hz, 6H); MS (ESI(-)) m/e 374 (M-H)\
Example 432
N- {4-[l -(4-methylbenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 278, substituting 4- methylbenzoyl chloride for acetyl chloride and N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)isoindoline-2-carboxamide for 5-amino-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO-iie) δ ppm 8.38 (s, IH), 7.55-7.58 (m, 2H), 7.20-7.39 (m, 10H), 6.01-6.21 (m, IH), 4.77 (s, 4H), 3.93-
4.36 (m, 2H), 3.43-3.90 (m, 2H), 2.48-2.57 (m, 2H), 2.36 (s, 3H); MS (ESI(+)) m/e 438 (M+H)+.
Example 433
N-[4-(l -benzyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 429, substituting benzaldehyde for isobutyraldehyde. ¾ NMR (400 MHz, DMSO-i¾) δ ppm 8.36 (s, IH), 7.52- 7.55 (m, 2H), 7.20-7.42 (m, 11H), 6.06-6.08 (m, IH), 4.76-4.77 (bs, 4H), 3.58 (s, 2H), 3.04- 3.06 (m, 2H), 2.63 (t, J = 5.6 Hz, 2H), 2.42-2.49 (m, 2H); MS (ESI(+)) m/e 410 (M+H)+.
Example 440
N- { 4-[(propylamino)carbonyl]phenyl } -5-pyridin-3-yl- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 280, substituting pyridin-
3-ylboronic acid for lH-pyrazol-3-ylboronic acid and 5-bromo-N-[4- (propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 8.91 (dd, 7 = 2.4, 0.9 Hz, IH), 8.63 (s, IH), 8.58 (dd, 7 = 4.7, 1.6 Hz, IH), 8.27 (t, 7 = 5.6 Hz, IH), 8.10 (ddd, 7 = 7.9, 2.4, 1.6 Hz, IH), 7.73-7.79 (m, 3H), 7.65-7.70 (m, 3H), 7.48-7.53 (m, 2H), 4.79-4.91 (m, 4H), 3.15-3.23 (m, 2H), 1.54 (s, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 401 (M+H)+.
Example 441
N- { 4-[(propylamino)carbonyl]phenyl } -5-pyridin-4-yl- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 280, substituting pyridin-
4-ylboronic acid for lH-pyrazol-3-ylboronic acid and 5-bromo-N-[4- (propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-<i6) δ ppm 8.62-8.66 (m, 3H), 8.25 (t, 7 = 5.6 Hz, IH), 7.70-7.81 (m, 6H), 7.64-7.69 (m, 2H), 7.52 (d, 7 = 8.0 Hz, IH), 4.85-4.92 (m, 4H), 3.16-3.22 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H). MS (ESI(+)) m/e 401 (M+H)+.
Example 442
N5-(2-methoxyethyl)-N2-{4-[(propylarnino)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2,5- dicarboxamide
The title compound was prepared as described in Example 1C, substituting 2- methoxyethanamine for 3-phenylpropan-l -amine and 2-{ [4-
(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.61 (s, IH), 8.54 (d, 7 = 5.3 Hz, IH), 8.26 (t, 7 = 5.7 Hz, IH), 7.79-7.85 (m, 2H), 7.73-7.80 (m, 2H), 7.63-7.67 (m, 2H), 7.45 (d, 7 = 7.8 Hz, IH), 4.81-4.83 (bs, 4H), 3.39-3.51 (m, 4H), 3.27 (s, 3H), 3.03-3.22 (m, 2H), 1.46-1.59 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 425 (M+H)+.
Example 443
N-(4-cyanophenyl)-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1A, substituting 4- isocyanatobenzonitrile for methyl 4-isocyanatobenzoate. ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.83 (s, IH), 7.78-7.82 (m, 2H), 7.69-7.73 (m, 2H), 7.31-7.39 (m, 4H), 4.79-4.81 (bs, 4H); MS (ESI(+)) m/e 264 (M+H)+.
Example 444
N-[4-(trifluoromethyl)phenyi] - 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1A, substituting 1- isocyanato-4-(trifluoromethyl)benzene for methyl 4-isocyanatobenzoate. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.74 (s, 1H), 7.80-7.83 (m, 2H), 7.60-7.63 (m, 2H), 7.30-7.39 (m, 4H), 4.79-4.80 (bs, 4H); MS (ESI(+)) m/e 307 (M+H)+.
Example 450
5-(l ,2-dihydroxyethyl)-N- { 4-[(propylamino)carbonyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide
A suspension of N-[4-(propylcarbamoyl)phenyl]-5-vinyl-l,3-dihydro-2H-isoindole-2- carboxamid (0.03 g, 0.086 mmol) in tetrahydrofuran (1 ml) and 2-propanol (0.3 ml) was treated with osmium tetroxide (2.5% wt. % solution in 2-methyl-2-propanol) (0.108 ml, 8.59 μιηοΐ). The reaction mixture was treated with N-methylmorpholine-N-oxide (0.030 g, 0.258 mmol). The reaction mixture was allowed to stir at room temperature overnight, quenched with aqueous sodium sulfite solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. Hash chromatography provided the title compound. ¾ NMR (300 MHz, DMSO- d6) δ ρριη 8.55 (s, 1H), 8.25 (t, J = 5.7 Hz, 1H), 7.74-7.78 (m, 2H), 7.63-7.68 (m, 2H), 7.27- 7.33 (m, 3H), 5.24 (d, J = 4.2 Hz, 1H), 4.75-4.77 (bs, 4H), 4.70 (t, J = 5.8 Hz, 1H), 4.53-4.59 (m, 1H), 3.43 (t, J = 5.8 Hz, 2H), 3.16-3.23 (m, 2H), 1.42-1.63 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 384 (M+H)+.
Example 451
N-[4-(l-benzoylpiperidin-4-yl)butyl]-5-cyano-l,3-dihydro-2H-isoindole-2-carboxarnide
Example 451 A
tert-butyl 4-(4-(5-cyanoisoindoline-2-carboxamido)butyl)piperidine- 1 -carboxylate The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(4-aminobutyl)piperidine-l -carboxylate for 4-amino-N-propylbenzamide and isoindoline-5-carbonitrile for methyl isoindoline-5-carboxylate hydrochloride.
Example 45 IB
5-cyano-N-(4-(piperidin-4-yl)butyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(5-cyanoisoindoline-2-carboxamido)butyl)piperidine-l -carboxylate for tert-butyl 4-((4- (5 -fluoroisoindoline-2 -carboxamido)benzamido)methyl)benzylcarbamate .
Example 451C
N-[4-(l-benzoylpiperidin-4-yl)butyl]-5-cyano-l,3-dihydro-2H-isoindole-2-carboxarnide The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and 5-cyano-N-(4-(piperidin-4-yl)butyl)isoindoline-2- carboxamide for 5-arnino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.83 (s, 1H), 7.75 (dd, J = 7.9, 1.5 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.41-7.44 (m, 3H), 7.31-7.38 (m, 2H), 6.36 (t, J = 5.5 Hz, 1H), 4.60-4.64 (m, 4H), 4.30-4.53 (m, IH), 3.42-3.71 (m, IH), 3.02-3.10 (m, 2H), 2.64-3.00 (m, 2H), 1.56-1.84 (m, 2H), 1.37-1.54 (m, 3H), 1.24-1.31 (m, 4H), 0.93-1.16 (m, 2H); MS (ESI(+)) m/e 431 (M+H)+.
Example 452
N-(r-butyryl-1^2^3^6'-tetrahydro-3,4'-bipyridin-6-yl)-1 -dihydro-2H-isoindole-2- carboxamide
Example 452A
N-(5-bromopyridin-2-yl)isoindoline-2-carboxamide
The tide compound was prepared as described in Example 344A, substituting 5- bromopyridin-2-amine for tert-butyl 5-aminoisoindoline-2-carboxylate.
Example 452B
tert-butyl 4-(6-(isoindoline-2-carboxamido)pyridin-3-yl)-5,6-dihydropyridine-l(2H)- carboxylate
The title compound was prepared as described in Example 280, substituting tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate for lH-pyrazol-3-ylboronic acid and N-(5-bromopyridin-2-yl)isoindoline-2-carboxamide for 5- bromo-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide.
Example 452C
N-(5-(l,2 ,6-tetrahydropyridin-4-yl)pyridin-2-yl)isoindoline-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl
4-(6-(isoindoline-2-carboxarrddo)pyridin-3-yl)-5,6-dmydropyridine-l(2H)-carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate.
Example 452D
N-(r-butyryl-l',2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting butyryl chloride for acetyl chloride and N-(5-(l,2,3,6-tetrahydropyridin-4-yl)pyridin-2-yl)isoindoline- 2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (500 MHz, DMSO- ) δ ppm 8.92-8.95 (bs, IH), 8.32-8.35 (m, IH), 7.64-7.97 (m, 2H), 6.94-7.38 (m, 4H), 6.16-6.22 (bs, IH), 4.45-5.02 (m, 4H), 4.08-4.15 (m, 2H), 3.62-3.68 (m,
2H), 2.23-2.65 (m, 4H), 1.46-1.64 (m, 2H), 0.87-0.93 (m, 3H); MS (ESI(+)) m/e 391 (M+H)+. Table 6.
The title compound was prepared as described in Example 1C, substituting N-(5- (l,2,3,6-tetrahydropyridin-4-yl)pyridin-2-yl)isoindoline-2-carboxamide for 3-phenylpropan- 1 -amine and the appropriate carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid.
Figure imgf000779_0001
r,2',3',6'-tetrahydro- 1H), 8.33-8.38 (m, IH), 7.79-7.92 (m, 2H), 7.27-7.36 m/e 391 3,4'-bipyridin-6-yl)-l,3- (m, 3H), 6.17-6.22 (bs, IH), 4.76-4.83 (bs, 4H), 4.07- (M+H)+ dihydro-2H-isoindole-2- 4.22 (m, 2H), 3.64-3.73 (m, IH), 2.84-2.98 (m, IH), carboxamide 2.37-2.63 (m, 3H), 0.77-1.20 (m, 6H)
454 N-[1'-((3R)- ¾ NMR (500 MHz, DMSO- ) δ ppm 8.92-8.95 (bs, (ESI(+)) tetrahydrofuran- 3 - IH), 8.32-8.36 (bs, IH), 7.79-7.92 (m, 2H), 7.11-7.51 m/e 419 ylcarbonyl)-l',2',3',6'- (m, 4H), 6.17-6.21 (bs, IH), 4.59-5.04 (m, 4H), 4.10- (M+H)+ tetrahydro-3,4'- 4.22 (m, 2H), 3.82-4.01 (m, IH), 3.59-3.81 (m, 5H), bipyridin-6-yl] -1,3- 2.33-2.62 (m, 2H), 1.94-2.15 (m, 2H)
dihydro-2H-isoindole-2- carboxamide
495 N-(l'-benzoyl-r,2',3',6'- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ ppm (ESI(+)) tetrahydro-3,4'- 8.51 (bs, IH), 8.32 (d, 7 = 2.5 Hz, IH), 7.90 (d, 7 = m/e 425 bipyridin-6-yl) -1,3- 8.7 Hz, IH), 7.77 (dd, 7 = 8.7, 2.5 Hz, IH), 7.48 - (M+H)+ dihydro-2H-isoindole-2- 7.39 (m, 5H), 7.36 - 7.25 (m, 4H), 6.16 (bs, IH), 4.81 carboxamide (s, 4H), 4.18 (m, 2H), 3.68 (m, 2H), 2.55 (m, 2H)
764 N- [ 1 '-(tetrahydrofuran- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+))
2-ylcarbonyl)-l',2',3',6'- 8.52 (bs, IH), 8.32 (d, 7 = 2.5 Hz, IH), 7.91 (m, IH), m/e 419 tetrahydro-3,4'- 7.76 (dd, 7 = 8.7, 2.5 Hz, IH), 7.37 - 7.26 (m, 4H), (M+H)+ bipyridin-6-yl] -1,3- 6.16 (m, IH), 4.82 (s, 4H), 4.68 (dd, 7 = 7.6, 5.6 Hz, dihydro-2H-isoindole-2- IH), 4.17 (m, 2H), 3.86 - 3.70 (m, 4H), 2.52 (m, 2H), carboxamide 2.12 (m, IH), 2.01 (m, IH), 1.87 (m, 2H)
765 N-[l'-(tetrahydro-2H- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) pyran-4-ylcarbonyl)- 8.52 (s, IH), 8.32 (d, 7 = 2.5 Hz, IH), 7.91 (d, 7 = 8.7 m/e 433 r,2',3',6'-tetrahydro- Hz, IH), 7.77 (dd, 7 = 8.7, 2.5 Hz, IH), 7.37 - 7.26 (M+H)+
3,4'-bipyridin-6-yl]-l,3- (m, 4H), 6.16 (m, IH), 4.82 (s, 4H), 4.17 (m, 2H),
dihydro-2H-isoindole-2- 3.87 (m, 2H), 3.72 (t, 7 = 5.7 Hz, 2H), 3.43 (td, J =
carboxamide 11.4, 2.6 Hz, 2H), 2.92 (m IH), 2.52 (m, 2H), 1.74 - 1.60 (m, 2H), 1.62 - 1.53 (m, 2H)
766 N-[l'-(l,4-dioxan-2- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) ylcarbonyl)-l',2',3',6'- 8.52 (s, IH), 8.32 (d, J = 2.2 Hz, IH), 7.91 (d, J = 8.8 m/e 435 tetrahydro-3,4'- Hz, IH), 7.76 (dd, J = 8.8, 2.5 Hz, IH), 7.40 - 7.23 (M+H)+ bipyridin-6-yl] -1,3- (m, 4H), 6.15 (m, IH), 4.82 (s, 4H), 4.38 (dd, 7 = 9.2, dihydro-2H-isoindole-2- 2.9 Hz, IH), 4.16 (m, 2H), 3.83 - 3.61 (m, 7H), 3.53 carboxamide (m, IH), 2.53(m, 2H)
767 N-{ 1'-[(1- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) methylpyrrolidin- 3 - 8.54 (m, IH), 8.31 (dd, 7 = 2.5, 0.8 Hz, IH), 7.90 (dd, m/e 432 yl)carbonyl]-r,2',3',6'- 7 = 8.7, 0.8 Hz, IH), 7.75 (dd, 7 = 8.7, 2.5 Hz, IH), (M+H)+ tetrahydro-3,4'- 7.36 - 7.25 (m, 4H), 6.15 (m, IH), 4.81 (s, 4H), 4.13 bipyridin-6-yl } - 1 ,3- (m, 2H), 3.69 (t, 7 = 5.7 Hz, 2H), 3.26 (m, IH), 2.77
dihydro-2H-isoindole-2- (t, 7 = 8.6 Hz, IH), 2.68 - 2.53 (m, 4H), 2.38 (m, IH), carboxamide 2.24 (s, 3H), 2.13 - 1.92 (m, 2H)
768 N-{ 1'-[(U- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) dioxidotetrahydrothioph 8.53 (bs, IH), 8.33 (d, 7 = 2.5 Hz, IH), 7.91 (d, 7 = m/e 467 en-3-yl)carbonyl]- 8.7 Hz, IH), 7.77 (dd, 7 = 8.7, 2.5 Hz, IH), 7.37 - (M+H)+ r,2',3',6'-tetrahydro- 7.26 (m, 4H), 6.16 (m, IH), 4.82 (s, 4H), 4.19 (m,
3,4'-bipyridin-6-yl}-l,3- 2H), 3.74 (m, 3H), 3.33 - 3.05 (m, 4H), 2.55 (m, 2H), dihydro-2H-isoindole-2- 2.37 (m, IH), 2.15 (m, IH)
carboxamide
769 N-[l'-(2-hydroxy-2- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) methylpropanoyl)- 8.51 (bs, IH), 8.31 (d, 7 = 2.5 Hz, IH), 7.90 (d, 7 = m/e 407 r,2',3',6'-tetrahydro- 8.7 Hz, IH), 7.76 (dd, 7 = 8.7, 2.5 Hz, IH), 7.36 - (M+H)+
3,4'-bipyridin-6-yl]-l,3- 7.25 (m, 4H), 6.17 (m, IH), 5.11 (bs, IH), 4.81 (s,
dihydro-2H-isoindole-2- 4H), 4.30 (m, 2H), 3.94 (m, 2H), 2.51 (m, 2H), 1.37 carboxamide (s, 6H)
801 N- [ l'-(morpholin-4- ¾ NMR (400 MHz, DMSO-<¾, Temp=90 °C) δ ppm (ESI(+)) ylacetyl)-l',2',3',6'- 8.51 (s, 1H), 8.32 (d, 7 = 2.5 Hz, 1H), 7.90 (d, 7 = 8.7 m/e 448 tetrahydro-3,4'- Hz, 1H), 7.76 (dd, 7 = 8.7, 2.5 Hz, 1H), 7.36 - 7.26 (M+H)+ bipyridin-6-yl] -1,3- (m, 4H), 6.15 (m, 1H), 4.81 (s, 4H), 4.13 (m, 2H), dihydro-2H-isoindole-2- 3.73 (m, 2H), 3.58 (m, 4H), 3.21 (s, 2H), 2.48 (m, carboxamide 2H), 2.45 (m, 4H)
Example 455
N-[2-(4-acetylpiperazin- 1 -yl)- lH-benzimidazol-5-yl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting N-[2- (piperazin-l-yl)-lH-benzirnidazol-6-yl]-l,3-dihydro-2H-isoindole-2-carboxarnide for 5- amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (500 MHz,
DMSO- , Temp=90°C) δ ppm 11.01-11.10 (bs, 1H), 7.89-7.91 (bs, 1H), 7.44-7.52 (m, 1H), 7.32-7.35 (m, 2H), 7.27-7.31 (m, 2H), 7.03-7.06 (m, 2H), 4.76 (s, 4H), 3.55-3.62 (m, 4H), 3.46-3.51 (m, 4H), 2.04 (s, 3H); MS (ESI(+)) m/e 405 (M+H)+.
Table 7.
The following Examples were essentially prepared as described in Example 1C, substituting the appropriate tetrahdropyridine for 3-phenylpropan-l -amine and the appropriate carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic
Figure imgf000781_0001
Figure imgf000782_0001
Figure imgf000783_0001
Figure imgf000784_0001
Figure imgf000785_0001
yl)propanoyl]-l,2,3,6- ppm 8.12-8.13 (bs, IH), 7.84-7.86 (m, 2H), 7.35- m/e 459 tetrahydropyridin-4- 7.38 (m, 2H), 7.21-7.25 (m, 2H), 7.16-7.20 (m, (M+H)+ yl } pheny 1) - 1 , 3 -dihydro - 2H), 5.94-5.98 (m, IH), 4.84-4.89 (m, 4H), 4.06- 2H-isoindole-2- 4.29 (m, 2H), 3.53-3.89 (m, 2H), 3.30 (t, 7 = 7.2
carboxamide Hz, 2H), 2.95-3.05 (m, 2H), 2.89-2.92 (m, 4H),
2.42-2.48 (m, 2H), 1.65-1.73 (m, 4H), 1.30-1.40
(m, 2H)
493 N-{4-[l-(morpholin-4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ (ESI(+)) ylacetyl)- 1,2,3,6- ppm 8.13-8.14 (bs, IH), 7.85-7.88 (m, 2H), 7.39- m/e 447 tetrahydropyridin-4- 7.41 (m, 2H), 7.20-7.24 (m, 2H), 7.16-7.20 (m, (M+H)+ y 1] phenyl } - 1 , 3 -dihydro - 2H), 6.01 -6.04 (m, IH), 4.86-4.87 (m, 4H), 4.27 (q,
2H-isoindole-2- 7 = 2.9 Hz, 2H), 3.75-3.80 (m, 2H), 3.64-3.72 (m, carboxamide 4H), 3.29 (s, 2H), 2.54-2.57 (m, 6H)
494 N-(4-{ l-[(4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ (ESI(+)) methylpiperazin- 1 - ppm 8.13-8.15 (bs, IH), 7.85-7.87 (m, 2H), 7.38- m/e 460 yl)acetyl] - 1,2,3,6- 7.41 (m, 2H), 7.20-7.25 (m, 2H), 7.19 (d, 7 = 7.0 (M+H)+ tetrahydropyridin-4- Hz, IH), 7.17-7.19 (m, IH), 6.00-6.02 (m, IH),
y 1 } pheny 1) - 1 , 3 -dihydro - 4.83-4.89 (m, 4H), 4.24-4.26 (m, 2H), 3.74-3.77
2H-isoindole-2- (m, 2H), 3.33 (s, 2H), 2.73-2.76 (m, 4H), 2.66-2.69 carboxamide (m, 4H), 2.49-2.54 (m, 2H), 2.36 (s, 3H)
759 N- { 4- [ 1 -(tetrahydro-2H- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) pyran-4-ylcarbonyl)- ppm 8.13 (s, IH), 7.54 (m, 2Ή), 7.38 - 7.23 (m, m/e 432
1 ,2,3,6-tetrahydropyridin- 6H), 6.08 (m, IH), 4.79 (d, 7 = 13.1 Hz, 4H), 4.15 (M+H)+
4-yl]phenyl}-l,3- (m, 2H), 3.86 (m, 2H), 3.70 (t, 7 = 5.7 Hz, 2H),
dihydro-2H-isoindole-2- 3.43 (td, 7 = 11.4, 2.4 Hz, 2H), 2.90 (m, IH), 2.50 carboxamide (m, 2H), 1.76 - 1.51 (m, 4H)
760 N-{4-[l-(l,4-dioxan-2- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) y lc arbonyl) -1,2,3,6- ppm 8.13 (s, IH), 7.55 (m, 2Ή), 7.38 - 7.26 (m, m/e 434 tetrahydropyridin-4- 6H), 6.07 (m, IH), 4.79 (m, 4H), 4.37 (dd, 7 = 9.2, (M+H)+ y 1] phenyl } - 1 , 3 -dihydro - 3.0 Hz, IH), 4.15 (m, 2H), 3.82 - 3.62 (m, 7H),
2H-isoindole-2- 3.53 (m, IH), 2.50 (m, 2H)
carboxamide
761 N-(4-{ l-[(l- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) methylpyrrolidin-3 - ppm 8.13 (s, IH), 7.54 (d, 7 = 8.6 Hz, 2H), 7.40 - m/e 431 yl)carbonyl]-l,2,3,6- 7.20 (m, 6H), 6.07 (s, IH), 4.78 (s, 4H), 4.12 (m, (M+H)+ tetrahydropyridin-4- 2H), 3.68 (t, 7 = 5.7 Hz, 2H), 3.27 (m, IH), 2.77
y 1 } pheny 1) - 1 , 3 -dihydro - (m, IH), 2.63 - 2.45 (m, 4H), 2.38 (m, IH), 2.25 (s,
2H-isoindole-2- 3H), 98 (m, 2H)
carboxamide
762 N-(4-{ l-[(l,l- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) dioxidotetrahydrothiophe ppm 8.14 (s, IH), 7.55 (m, 2Ή , 7.38 - 7.27 (m, m/e 466 n-3-yl)carbonyl]-l,2,3,6- 6H), 6.08 (m, IH), 4.81 (m, 4H), 4.17 (m, 2H), 3.74 (M+H)+ tetrahydropyridin-4- (m, 3H), 3.33 - 3.10 (m, 3H), 3.07 (m, IH), 2.53
y 1 } pheny 1) - 1 , 3 -dihydro - (m, 2H), 2.37 (m, IH), 2.14 (m, IH)
2H-isoindole-2- carboxamide
763 N-{4-[l-(2-hydroxy-2- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) methylpropanoyl)- ppm 8.13 (s, IH), 7.54 (m, 2Ή , 7.38 - 7.27 (m, m/e 406
1 ,2,3,6-tetrahydropyridin- 6H), 6.09(m, IH), 5.10 (s, IH), 4.78 (s, 4H), 4.28 (M+H)+
4-yl]phenyl}-l,3- (m, 2H), 3.94 (m, 2H), 2.50 (m, 2H), 1.37 (s, 6H) dihydro-2H-isoindole-2- carboxamide
1019 5-cyano-N- {4-[l-(2- - ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) methylpropanoyl)- ppm 8.20 (m, IH), 7.80 (m, IH), 7.70 (m, IH), 7.54 m/e 415 1 ,2,3,6-tetrahydropyridin- (m, 3H), 7.37 (m, 2H), 6.08 (bs, 1H), 4.90 (m, 4H), (M+H)+ 4-yl]phenyl}-l,3- 4.13 (m, 2H), 3.69 (m, 2H), 2.90 (m, 1H), 2.50 (m, dihydro-2H-isoindole-2- 2H), 1.02 (m, 6H)
carboxamide
1281 5-cyano-N-{4-[l- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+))
(tetrahydrofuran-3- ppm 8.21 (s, 1H), 7.80 (s, 1H), 7.71 (d, 7= 7.9 Hz, m/e 443 ylc arbonyl) -1,2,3,6- 1H), 7.54 (m, 3H), 7.33 (m, 2H), 6.07 (bs, 1H), (M+H)+ tetrahydropyridin-4- 4.83 (m, 4H), 4.14 (m, 2H), 3.91 (t, 7 = 8.1 Hz,
yl] phenyl } - 1 , 3 -dihydro - 1H), 3.71 (m, 5H), 3.38 (m, 1H), 2.50 (m, 2H), 2.07
2H-isoindole-2- (m, 2H)
carboxamide
1282 5-cyano-N-{4-[l- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+))
(tetrahydro-2H-pyran-4- ppm 8.22 (bs, 1H), 7.80 (s, IH), 7.72 (d, 7 = 7.8 m/e 457 ylc arbonyl) -1,2,3,6- Hz, IH), 7.54 (m, 3H), 7.33 (m, 2H), 6.08 (bs, IH), (M+H)+ tetrahydropyridin-4- 4.82 (m, 4H), 4.14 (m, 2H), 3.86 (m, 2H), 3.70 (t, 7 yl] phenyl } - 1 , 3 -dihydro - = 5.7 Hz, 2H), 3.42 (td, 7 = 11.4, 2.5 Hz, 2H), 2.90
2H-isoindole-2- (m, IH), 2.50 (m, 2H), 1.77 - 1.53 (m, 4H)
carboxamide
1283 5-cyano-N-{4-[l-(2- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) hydroxy-2- ppm 8.21 (s, IH), 7.80 (s, 1H), 7.71 (d, 7= 7.7 Hz, m/e 431 methylpropanoyl)- IH), 7.53 (m, 3H), 7.33 (m, 2H), 6.08 (m, IH), 5.10 (M+H)+
1 ,2,3,6-tetrahydropyridin- (s, IH), 4.83 (m, 4H), 4.28 (m, 2H), 3.93 (m, 2H),
4-yl]phenyl}-l,3- 2.50 (m, 2H), 1.37 (s, 6H)
dihydro-2H-isoindole-2- carboxamide
1284 5-cyano-N-{4-[l- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+))
(morpholin-4-ylacetyl)- ppm 8.21 (s, IH), 7.80 (s, IH), 7.72 (d, 7= 7.9 Hz, m/e 472
1 ,2,3,6-tetrahydropyridin- IH), 7.51 (m, 3H), 7.33 (m, 2H), 6.07 (m, IH), 4.83 (M+H)+
4-yl]phenyl}-l,3- (m, 4H), 4.15 (m, 2H), 3.71 (m, 2H), 3.58 (m, 4H), dihydro-2H-isoindole-2- 3.21 (s, 2H), 2.50 (m, 2H), 2.45 (m, 4H)
carboxamide
Example 495
N-(r-benzoyl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide
The tide compound was prepared as described in Example 1C, substituting N-(5- (l,2,3,6-tetrahydropyridin-4-yl)pyridin-2-yl)isoindoline-2-carboxamide for 3-phenylpropan- 1 -amine and benzoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO- Temp=90°C) δ ppm 8.51 (bs, IH), 8.32 (d, 7 = 2.5 Hz, IH), 7.90 (d, 7 = 8.7 Hz, IH), 7.77 (dd, 7= 8.7, 2.5 Hz, IH), 7.48 - 7.39 (m, 5H), 7.36 - 7.25 (m, 4H), 6.16 (bs, IH), 4.81 (s, 4H), 4.18 (m, 2H), 3.68 (m, 2H), 2.55 (m, 2H); MS (ESI(+)) m/e 425 (M+H)+.
Example 496
N-(4- { [6-(benzoylamino)hexyl]carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-{4-[(6-aminohexyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.57 (s, IH), 8.43 (t, 7 = 5.6 Hz, IH), 8.25 (t, 7= 5.6 Hz, IH), 7.81-7.86 (m, 2H), 7.74-7.78 (m, 2H), 7.63-7.67 (m, 2H), 7.41-7.54 (m, 3H), 7.29-7.39 (m, 4H), 4.78-4.79 (bs, 4H), 3.15-3.27 (m, 4H), 1.44-1.64 (m, 4H), 1.19- 1.39 (m, 4H); MS (ESI(+)) m/e 485 (M+H)+.
Example 497
N- [4-( { 4- [(benzoylamino)methyl]benzyl } carbamoyl)phenyl] -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide
The tide compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(4-{ [4-(aminomethyl)benzyl]carbamoyl}phenyl)-5-fluoro- l ,3-dihydro-2H-isoindole-2-carboxamide for 5-amino-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-iie) δ ppm 9.01 (t, 7 = 6.0 Hz, 1H), 8.83 (t, 7 = 5.9 Hz, 1H), 8.60 (s, 1H), 7.85-7.91 (m, 2H), 7.78-7.83
(m, 2H), 7.63-7.68 (m, 2H), 7.36-7.56 (m, 4H), 7.27 (s, 4H), 7.21-7.26 (m, 1H), 7.10-7.19 (m, 1H), 4.72-4.81 (m, 4H), 4.40-4.48 (m, 4H); MS (ESI(+)) m/e 523 (M+H)+.
Table 8.
The following Examples were essentially prepared as described in Example 1C, substituting N-(4-(piperazin-l-yl)phenyl)isoindoline-2-carboxamide for 3-phenylpropan-l- amine and the appropriate carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid.
Figure imgf000788_0001
2-carboxamide
503 N-[4-(4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+)) butyrylpiperazin- 1 - 7.91-7.93 (m, 1H), 7.73-7.77 (m, 2H), 7.20-7.23 (m, m/e 393 yl)phenyl]-l,3- 2H), 7.19 (d, 7 = 7.3 Hz, 1H), 7.17-7.18 (m, 1H), (M+H)+ dihydro-2H-isoindole- 6.93-6.96 (m, 2H), 4.86 (s, 4H), 3.48-3.70 (m, 3H),
2-carboxamide 3.02-3.06 (m, 4H), 2.43 (d, J = 0.6 Hz, 1H), 2.31 (t, J
= 7.3 Hz, 2H), 1.65-1.81 (m, 2H), 0.95 (t, J = 7.3 Hz,
3H)
504 N-[4-(4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+)) isobutyrylpiperazin- 1 - 7.92-7.94 (bs, 1H), 7.74-7.76 (m, 2H), 7.20-7.23 (m, m/e 393 yl)phenyl]-l,3- 2H), 7.16-7.20 (m, 2H), 6.93-6.96 (m, 2H), 4.86 (s, (M+H)+ dihydro-2H-isoindole- 4H), 3.65-3.69 (m, 4H), 3.03-3.06 (m, 4H), 2.76-2.87
2-carboxamide (m, 1H), 1.15 (d, J = 6.7 Hz, 6H)
505 N-{4-[4-(2- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+)) methylbutanoyl)pipera 7.92-7.94 (bs, 1H), 7.74-7.77 (m, 2H), 7.20-7.23 (m, m/e 407 zin- 1 - yl] phenyl } - 1 , 3 - 2H), 7.16-7.20 (m, 2H), 6.94-6.97 (m, 2H), 4.86 (s, (M+H)+ dihydro-2H-isoindole- 4H), 3.68-3.73 (m, 4H), 3.04-3.07 (m, 4H), 2.68 (h, J
2-carboxamide = 6.7 Hz, 1H), 1.76-1.87 (m, 1H), 1.40-1.51 (m, 1H),
1.15 (d, J = 6.7 Hz, 3H), 0.91 (t, J = 7.4 Hz, 3H)
506 N-{4-[4-(3,3,3- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+)) trifluoropropanoyl)pip 7.93-7.95 (bs, 1H), 7.74-7.76 (m, 2H), 7.20-7.24 (m, m/e 433 erazin- 1 -yl] phenyl } - 2H), 7.16-7.19 (m, 2H), 6.92-6.95 (m, 2H), 4.86 (s, (M+H)+ l,3-dihydro-2H- 4H), 3.58-3.78 (m, 4H), 3.57 (q, J = 10.5 Hz, 2H),
isoindole-2- 3.02-3.09 (m, 4H)
carboxamide
507 N-{4-[4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+))
(methoxyacetyl)pipera 7.92-7.96 (bs, 1H), 7.73-7.76 (m, 2H), 7.16-7.24 (m, m/e 395 zin- 1 - yl] phenyl } - 1 , 3 - 4H), 6.92-6.95 (m, 2H), 4.86 (s, 4H), 4.18 (s, 2H), (M+H)+ dihydro-2H-isoindole- 3.55-3.78 (m, 4H), 3.39 (s, 3H), 3.03-3.06 (m, 4H)
2-carboxamide
508 N-{4-[4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+))
(tetrahydrofuran-2- 7.90-7.95 (m, 1H), 7.73-7.75 (m, 2H), 7.19-7.24 (m, m/e 421 ylcarbonyl)piperazin- 2H), 7.15-7.19 (m, 2H), 6.92-6.95 (m, 2H), 4.86 (s, (M+H)+
1- yl]phenyl}-l,3- 4H), 4.66 (dd, J = 7.2, 5.4 Hz, 1H), 3.88-3.94 (m,
dihydro-2H-isoindole- 1H), 3.67-3.83 (m, 5H), 2.93-3.15 (m, 4H), 2.37-2.48
2- carboxamide (m, 1H), 1.84-2.05 (m, 2H), 1.70-1.81 (m, 1H)
509 N-{4-[4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+))
(tetrahydrofuran-3- 7.93 (d, J = 2.6 Hz, 1H), 7.74-7.77 (m, 2H), 7.20-7.24 m/e 421 ylcarbonyl)piperazin- (m, 2H), 7.15-7.20 (m, 2H), 6.94-6.97 (m, 2H), 4.86 (M+H)+
1- yl]phenyl}-l,3- (s, 4H), 4.08 (dd, J = 8.3, 6.5 Hz, 1H), 4.04 (t, J = 8.0 dihydro-2H-isoindole- Hz, 1H), 3.91 (td, J = 7.9, 5.9 Hz, 1H), 3.74-3.82 (m,
2- carboxamide 1H), 3.58-3.76 (m, 4H), 3.26-3.34 (m, 1H), 3.00-3.10
(m, 4H), 2.24-2.33 (m, 1H), 1.97-2.07 (m, 1H)
510 N-{4-[4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+))
(cyclopentylacetyl)pip 7.90-7.92 (bs, 1H), 7.73-7.76 (m, 2H), 7.19-7.24 (m, m/e 433 erazin- 1 -yl] phenyl } - 2H), 7.15-7.19 (m, 2H), 6.94-6.97 (m, 2H), 4.85 (s, (M+H)+ l,3-dihydro-2H- 4H), 3.46-3.83 (m, 4H), 3.04-3.07 (m, 4H), 2.28-2.49 isoindole-2- (m, 3H), 1.81-1.96 (m, 2H), 1.41-1.67 (m, 4H), 1.17- carboxamide 1.32 (m, 2H)
511 N-{4-[4- ¾ NMR (400 MHz, Pyridine-^, Temp=90°C) δ ppm (ESI(+))
(cyclohexylcarbonyl)p 7.90-7.92 (bs, 1H), 7.73-7.76 (m, 2H), 7.20-7.24 (m, m/e 433 iperazin- 1 -yl] phenyl } - 2H), 7.15-7.20 (m, 2H), 6.94-6.97 (m, 2H), 4.86 (s, (M+H)+ l,3-dihydro-2H- 4H), 3.64-3.77 (m, 4H), 3.04-3.07 (m, 4H), 2.60 (tt, J
isoindole-2- = 11.0, 3.5 Hz, 1H), 1.55-1.85 (m, 7H), 1.14-1.40 (m,
Figure imgf000790_0001
Figure imgf000791_0001
Figure imgf000792_0001
Figure imgf000793_0001
Example 542
5-cyano-N-(4-phenylbutyl)-l,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1A, substituting 4- phenylbutyl isocyanate for methyl 4-isocyanatobenzoate and 5-cyanoisoindoline for isoindoline. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.82 (s, 1H), 7.74 (dd, J = 7.9, 1.5 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.24-7.31 (m, 2H), 7.08-7.22 (m, 3H), 6.38 (t, 7 = 5.6 Hz, 1H), 4.59-4.64 (m, 4H), 3.06-3.13 (m, 2H), 2.58 (t, 7 = 7.5 Hz, 2H), 1.53-1.68 (m, 2H), 1.36-1.51 (m, 2H); MS (ESI(+)) m/e 319 (M+H)+.
Example 543
N-[4-(l -butyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
Example 543A
N-(4-bromophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide
The title compound was prepared as described in Example 1A, substituting 4- bromophenyl isocyanate for methyl 4-isocyanatobenzoate and 2,3-dihydro-lH-pyrrolo[3,4- c]pyridine for isoindoline.
Example 543B
tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)-5,6- dihydropyridine- 1 (2H)-carboxylate
The title compound was prepared as described in Example 280, substituting tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate for lH-pyrazol-3-ylboronic acid and N-(4-bromophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 5-bromo-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide.
Example 543C
N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)-5,6-dihydropyridine- l(2H)-carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate. Example 543D
N-[4-(l -butyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 278, substituting butyryl chloride for acetyl chloride and N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4- c]pyridine-2(3H)-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.61 (s, IH), 8.50 (d, J = 5.0 Hz, IH), 8.46 (s, IH), 7.54-7.57 (m, 2H), 7.43 (d, 7 = 5.0 Hz, IH), 7.32-7.39 (m, 2H), 6.09-6.11 (m, IH), 4.79-4.82 (m, 4H), 4.08-4.14 (m, 2H), 3.58-3.68 (m, 2H), 2.39-2.55 (m, 2H), 2.34 (dt, 7 = 19.9, 7.4 Hz, 2H), 1.47-1.62 (m, 2H), 0.88-0.93 (m, 3H); MS (ESI(+)) m/e 391 (M+H)+.
Example 544
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 278, substituting isobutyryl chloride for acetyl chloride and N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)-lH- pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 5-amino-N-(4-
(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO-iie) δ ppm 8.61 (s, IH), 8.50 (d, J = 5.0 Hz, IH), 8.46 (s, IH), 7.54-7.57 (m, 2H), 7.43 (d, 7 = 5.1 Hz, IH), 7.34-7.38 (m, 2H), 6.10-6.13 (bs, IH), 4.79-4.82 (m, 4H), 4.07-4.21 (m, 2H), 3.67-3.70 (m, 2H), 2.85-3.01 (m, IH), 2.39-2.55 (m, 2H), 0.97-1.08 (m, 6H); MS (ESI(+)) m/e 391 (M+H)+.
Example 545
N-[4-(l -benzoyl- 1,2,3, 6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4- c]pyridine-2(3H)-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.61 (s, IH), 8.50 (d, 7 = 5.0 Hz, IH), 8.46 (s, IH), 7.55-7.58 (m, 2H), 7.42-7.49 (m, 6H), 7.35-7.41 (m, 2H), 5.98-6.21 (m, IH), 4.79-4.82 (m, 4H), 3.95-4.39 (m, 2H), 3.79-3.93 (m, IH), 3.51-3.61 (m, IH), 2.46-2.60 (m, 2H); MS (ESI(+)) m/e 425 (M+H)+.
Table 9.
The following Examples were essentially prepared as described in Example 1C, substituting N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and the corresponding carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid.
Figure imgf000795_0001
y ro- -pyrroo , - , . m, , . m, , . m, ,
Figure imgf000796_0001
Figure imgf000797_0001
Figure imgf000798_0001
Figure imgf000799_0001
Figure imgf000800_0001
y ro- -pyrroo , - 4.14 (s, 2 H) 3.70 (t, 7=5.80 Hz, 2 H) 3.02 (m,
Figure imgf000801_0001
Figure imgf000802_0001
Figure imgf000803_0001
yl)propanoyl]-l,2,3,6- ppm 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.48 - m/e 446 tetrahydropyridin-4- 7.53 (m, 2 H) 7.41 (d, 7=4.88 Hz, 1 H) 7.31 - 7.36 (M+H)+ yl } pheny 1) - 1 , 3 -dihydro - (m, 2 H) 6.09 (t, 7=3.51 Hz, 1 H) 4.81 (d, 7=7.02
2H-pyrrolo[3,4- Hz, 4 H) 4.21 (s, 2 H) 3.69 - 3.88 (m, 2 H) 3.61 - c]pyridine-2-carboxamide 3.70 (m, 1 H) 2.53 - 2.66 (m, 4 H) 2.43 - 2.50 (m,
2 H) 1.63 - 1.73 (m, 4 H) 1.19 (d, 7=6.71 Hz, 3 H)
N-(4-{ l-[(l,3-dimethyl- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C)8 (ESI(+)) lH-pyrazol-4- ppm 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.78 (s, m/e 443 yl)carbonyl]-l,2,3,6- 1 H) 7.52 (d, 7=8.54 Hz, 2 H) 7.41 (d, 7=4.88 Hz, (M+H)+ tetrahydropyridin-4- 1 H) 7.35 (d, 7=8.85 Hz, 2 H) 6.07 - 6.11 (m, 1 H) yl } pheny 1) - 1 , 3 -dihydro - 4.81 (d, 7=7.32 Hz, 4 H) 4.19 (d, 7=3.05 Hz, 2 H)
2H-pyrrolo[3,4- 3.77 - 3.79 (m, 3 H) 3.72 - 3.77 (m, 2 H) 2.52 - c]pyridine-2-carboxamide 2.57 (m, 2 H) 2.16 - 2.22 (m, 3 H)
Example 547
N-[4-(l -oxo-2, 3-dihydro-lH-isoindol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-phenyl)-2,3-dihydro- isoindol-l-one. ESI-MS [M+H+]= 370.1.
Example 548
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 377C, substituting isoindoline with 2,3-dihydro-lH-pyrrolo[3,4-c]pyridine. ESI-MS [M+H+]= 384.1.
Example 549
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide
The title compound was prepared as described in Example 377C, substituting isoindoline with 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine. ESI-MS [M+H+]= 384.1.
Example 550
N-[4-(l-oxo-l,2-dihydroisoquinolin-4-yl)cyclohex-3-en-l-yl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-cyclohex-l-enyl)-2H- isoquinolin-l-one. ESI-MS [M+H+]= 386.2.
Example 551
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)cyclohex-3-en- 1 -yl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-cyclohex-l-enyl)-2H- phthalazin-l-one. ESI-MS [M+H+]= 387.2. Example 552
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)cyclohex-3-en- 1 -yl] -5-(pyrrolidin-l -ylmethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 377C, substituting 4-(4- aminophenyl)-5,6,7,8-tetrahydro-2H-phthalazin-l-one with 4-(4-amino-cyclohex-l-enyl)-2H- phthalazin-l-one and isoindoline with 5-pyrrolidin-l-ylmethyl-2,3-dihydro-lH-isoindole. ESI-MS [M+H+]= 470.2.
Example 557
N- [ 1 -(3-methylbutyl)- 1 H-pyrazol-4-yl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting 1- isopentyl-lH-pyrazol-4-amine dihydrochloride for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride in Example 272B. ¾ NMR (300 MHz, DMSO-de) δ ppm 8.39 (s, 1H), 7.74 (s, 1H), 7.39 (s, 1H), 7.38 - 7.26 (m, 4H), 4.69 (s, 4H), 4.04 (t, 7 = 7.1 Hz, 2H), 1.81 - 1.57 (m, 2H), 1.52 - 1.37 (m, 1H), 0.89 (d, 7 = 6.6 Hz, 6H) ; MS (ESI(+)) m/e 299 (M+H)+.
Example 558
N- [1 -(2-phenylethyl)- 1 H-pyrazol-4-yl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting 1- phenethyl-lH-pyrazol-4-amine dihydrochloride for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride in Example 272B. ¾ NMR (300 MHz, DMSO-de) δ ppm 8.39 (s, 1H), 7.68 (s, 1H), 7.42 (s, 1H), 7.39 - 7.23 (m, 6H), 7.24 - 7.15 (m, 3H), 4.68 (bs, 4H), 4.27 (t, 7 = 7.3 Hz, 2H), 3.07 (t, 7 = 7.3 Hz, 2H); MS (ESI(+)) m e 333 (M+H)+.
Example 559
N5-[2-(dimethylamino)ethyl]-N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5- dicarboxamide
The title compound was prepared as described in Example 1C, substituting ΝΙ,ΝΙ- dimethylethane-l,2-diamine for 3-phenylpropan-l -amine and 2-{ [4- (propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 9.28 (s, 1H), 8.70 (t, 7 = 5.6 Hz, 1H), 8.62 (s, 1H), 8.26 (t, 7 = 5.6 Hz, 1H), 7.86 - 7.74 (m, 4H), 7.68 - 7.61 (m, 2H), 7.49 (d, 7 = 7.8 Hz, 1H), 4.84 (bs, 4H), 3.66 - 3.55 (m, 2H), 3.29 - 3.12 (m, 4H), 2.90 - 2.80 (m, 6H), 2.28 - 1.46 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 438 (M+H)+.
Example 560
5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide The title compound was prepared as described in Example 1C, substituting morpholine for 3-phenylpropan-l -amine and 2-{ [4-
(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 8.61 (s, 1H), 8.26 (t, J = 5.7 Hz, 1H), 7.80 - 7.73 (m, 2H), 7.69 - 7.62 (m, 2H), 7.47 - 7.41 (m, 2H), 7.35 (dd, J = 7.7, 1.6 Hz, 1H), 4.82 (bs, 4H), 3.73 - 3.43 (m, 6H), 3.28 - 3.12 (m, 4H), 1.60 - 1.44 (m, 2H), 0.89 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 437 (M+H)+.
Example 561
N-(4-{benzyl[3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting N-benzyl- 3-morpholinopropan-l-amine for 3-phenylpropan-l -amine. ¾ NMR (400 MHz, DMSO-(¾, Temp=90 °C) δ ppm 8.28 (s, 1H), 7.65 - 7.59 (m, 2H), 7.39 - 7.25 (m, 11H), 4.79 (bs, 4H), 4.63 (s, 2H), 3.52 - 3.45 (m, 4H), 3.35 - 3.27 (m, 2H), 2.27 - 2.20 (m, 4H), 2.17 (t, 2H), 1.69 - 1.60 (m, 2H) ; MS (ESI(+)) m/e 499 (M+H)+.
Example 563
5-bromo-N- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 563A
2 -cyclopentyl -N- (4 -nitrophenyl) acetamide
The title compound was prepared as described in Example 278, substituting 2- cyclopentylacetyl chloride for acetyl chloride and 4 -nitro aniline for 5-amino-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide.
Example 563B
N-(4-aminophenyl)-2-cyclopentylacetamide
The title compound was prepared as described in Example 274, substituting 2- cyclopentyl-N-(4-nitrophenyl)acetamide for 5-nitro-N-[4-(propylcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide.
Example 563C
5-bromo-N- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting N-(4- aminophenyl)-2-cyclopentylacetamide for 4-amino-N-propylbenzamide and 5- bromoisoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.68 (s, 1H), 8.29 (s, 1H), 7.65 - 7.55 (m, 1H), 7.53 - 7.36 (m, 5H), 7.36 - 7.26 (m, 1H), 4.79 - 4.65 (m, 4H), 2.33 - 2.16 (m, 3H), 1.85 - 1.68 (m, 2H), 1.68 - 1.41 (m, 4H), 1.29 - 1.09 (m, 2H); MS (ESI(+)) m/e 442 (M+H)+.
Example 565
methyl 4-{ [(5-cyano-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoate The title compound was prepared as described in Example 1A, substituting 5- cyanoisoindoline for isoindoline. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.81 (s, 1H), 7.91 - 7.82 (m, 3H), 7.82 - 7.77 (m, 1H), 7.76 - 7.69 (m, 2H), 7.59 (d, J = 7.9 Hz, 1H), 4.89 - 4.81 (m, 4H), 3.81 (s, 3H); MS (ESI(+)) m/e 322 (M+H)+.
Example 566
N-(4- { (E)-[(benzyloxy)irnino]methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 566A
N-(4-formylphenyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 272B, substituting 4- aminobenzaldehyde for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline- 5-carboxylate hydrochloride.
Example 566B
N-(4- { (E)-[(benzyloxy)imino]methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide In a 8 mL sealed vial was mixed N-(4-formylphenyl)isoindoline-2-carboxamide (50 mg, 0.188 mmol) in methanol (1 ml). A solution of O-benzylhydroxylamine hydrochloride (45.0 mg, 0.282 mmol) and sodium acetate (46.0 mg, 0.338 mmol) in water (1.000 ml) was then added and the reaction was stirred overnight at room temperature. The reaction was diluted with water and the product was extracted with dichloromethane. The organic layer was washed with brine, dried with sodium sulfate, decanted, and concentrated. Purification by chromatography provided the title compound. ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.55 (s, 1H), 8.21 (s, 1H), 7.65 (m, 2H), 7.50 (m, 2H), 7.44 - 7.28 (m, 9H), 5.14 (s, 2H), 4.78 (bs, 4H); MS (ESI(+)) m/e 372 (M+H)+.
Example 573
N- [4-(3-aminopyrrolidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 339D. ¾ NMR (400
MHz, DMSO- , Temp=90 °C) δ ppm 7.76 (bs, 1H), 7.36 - 7.31 (m, 2H), 7.31 - 7.25 (m, 4H), 6.46 - 6.42 (m, 2H), 4.73 (bs, 4H), 3.56 (p, J = 5.8 Hz, 1H), 3.41 - 3.36 (m, 1H), 3.35 - 3.28 (m, 1H), 3.24 - 3.15 (m, 3H), 2.85 (dd, 7 = 9.1, 4.9 Hz, 1H), 2.13 - 2.05 (m, 1H), 1.73 - 1.64 (m, 1H); MS (ESI(+)) m/e 323 (M+H)+.
Example 574
N-{6-[(3-memylbutyl)carbamoyl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2-carboxarnide
Example 574A
methyl 5-(isoindoline-2-carboxamido)picolinate The title compound was prepared as described in Example 272B, substituting methyl 5-aminopicolinate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5- carboxylate hydrochloride. Example 574B
5-(isoindoline-2-carboxamido)picolinic acid
The title compound was prepared as described in Example IB, substituting methyl 5- (isoindoline-2-carboxamido)picolinate for methyl 4-(isoindoline-2-carboxamido)benzoate.
Example 574C
N-{6-[(3-memylbutyl)carbamoyl]pyridin-3-yl}-1 -dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 3- methylbutan-1 -amine for 3-phenylpropan-l -amine and 5-(isoindoline-2- carboxamido)picolinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. H NMR (400 MHz, DMSO- ) δ ppm 8.85 (m, 2H), 8.57 (t, 7 = 6.1 Hz, 1H), 8.17 (dd, 7 = 8.5, 2.4 Hz, 1H),
7.94 (d, 7 = 8.5 Hz, 1H), 7.41 - 7.29 (m, 4H), 4.79 (m, 4H), 3.35 (m, 2H), 1.59 (m, 1H), 1.42 (q, 7 = 7.1 Hz, 2H), 0.90 (d, J = 6.6 Hz, 6H); MS (ESI(+)) m/e 353 (M+H)+.
Example 575
N- { 6-[(3-phenylpropyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 5-
(isoindoline-2-carboxamido)picolinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO- d6) δ ppm 8.86 (m, 2H), 8.68 (t, 7 = 6.0 Hz, 1H), 8.18 (dd, 7 = 8.6, 2.5 Hz, 1H), 7.95 (d, 7 = 8.5 Hz, 1H), 7.41 - 7.14 (m, 9H), 4.81 (bs, 4H), 3.35 (m, 2H), 2.61 (t, 7 = 7.6 Hz, 2H), 1.84 (m, 2H); MS (ESI(+)) m/e 401 (M+H)+.
Example 576
N- {6- [(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting
(tetrahydrofuran-3-yl)methanamine for 3-phenylpropan-l -amine and 5-(isoindoline-2- carboxamido)picolinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. H NMR (400
MHz, DMSO- ) δ ppm 8.87 (m, 2H), 8.78 (t, 7 = 6.1 Hz, 1H), 8.18 (dd, 7 = 8.5, 2.5 Hz, 1H),
7.95 (d, 7 = 8.5 Hz, 1H), 7.42 - 7.26 (m, 4H), 4.81 (m, 4H), 3.75 (m, 1H), 3.70 - 3.56 (m, 2H), 3.47 (dd, 7 = 8.5, 5.3 Hz, 1H), 3.27 (m, 2H), 2.53 (m, 1H), 1.91 (m, 1H), 1.61 (m, 1H); MS (ESI(+)) m/e 368 (M+H)+.
Example 577
N2- { 4- [(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2,5 -dicarboxamide The title compound was prepared as described in Example 132 susbtituting 5-cyano- N- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide for 5- cyano-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.69 (s, 1H), 8.31 (s, 1H), 7.98 (s, 1H), 7.87 - 7.78 (m, 2H), 7.53 - 7.38 (m, 5H), 7.36 (brs, 1H), 4.78 (bs, 4H), 2.32 - 2.13 (m, 3H), 1.82 - 1.67 (m, 2H), 1.67 - 1.42 (m, 4H), 1.27 - 1.10 (m, 2H); MS (ESI(+)) m/e 407 (M+H)+. Example 578
N-[4-({benzyl[3-(morpholin-4-yl)propyl] amino } methyl)phenyl]- 1 ,3-dihydro-2H-isoindole-2- carboxamide
To a stirring suspension of N-(4-{benzyl[3-(morpholin-4- yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2-carboxamide (0.028 g, 0.056 mmol) in THF (1.1 ml) was added 1M borane tetrahydrofuran complex (0.225 ml, 0.225 mmol) dropwise. The mixture was heated at 60°C for 5 hours. Additional borane complex (0.084 mL) was added and reaction was heated at 60 °C for 1 hour. The reaction was cooled to ambient temperature and 0.3 mL of 1.25 M HC1 in methanol was added. The quenched reaction was stirred 30 min and concentrated. The title compound was isolated after flash chromatography. ¾ NMR (400 MHz, pyridine- ds, Temp=90°C) δ ppm 8.05 (s, 1H), 7.88 - 7.82 (m, 2H), 7.47 - 7.38 (m, 4H), 7.36 - 7.29 (m, 2H), 7.26 - 7.15 (m, 5H), 4.85 (bs, 4H), 3.68 - 3.59 (m, 8H), 3.48 - 3.35 (m, 1H), 2.59 (t, J = 7.0 Hz, 2H), 2.38 - 2.29 (m, 6H), 1.79 - 1.65 (m, 3H); MS (ESI(+)) m/e 485 (M+H)+.
Example 579
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 280, substituting 5-bromo- N-(4-(2-cyclopentylacetamido)phenyl)isoindoline-2-carboxarnide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-(¾) δ ppm 13.30 (bs, 0.25H), 12.87 (bs, 0.75H), 9.69 (s, 1H), 8.34 - 8.23 (m, 1H), 7.83 - 7.63 (m, 3H), 7.56 - 7.32 (m, 5H), 6.76 - 6.68 (m, 1H), 4.81 - 4.72 (m, 4H), 2.31 - 2.12 (m, 3H), 1.85 - 1.67 (m, 2H), 1.67 - 1.42 (m, 4H), 1.29 - 1.10 (m, 2H); MS (ESI(+)) m/e 430 (M+H)+.
Example 580
N- {4-[(cyclopentylacetyl)amino]phenyl } -5-(pyridin-3-yl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 280, substituting pyridin- 3-ylboronic acid for lH-pyrazol-3-ylboronic acid and 5-bromo-N-(4-(2- cyclopentylacetamido)phenyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-(¾) δ ppm 9.70 (bs, 1H), 8.93 - 8.89 (m, 1H), 8.58 (dd, 7 = 4.7, 1.6 Hz, 1H), 8.33 (s, 1H), 8.13 - 8.05 (m, 1H), 7.72 (bs, 1H), 7.71 - 7.64 (m, 1H), 7.54 - 7.44 (m, 6H), 4.81 (bs, 4H), 2.31 - 2.18 (m, 3H), 1.82 - 1.68 (m, 2H), 1.68 - 1.43 (m, 4H), 1.26 - 1.11 (m, 2H); MS (ESI(+)) m/e 441 (M+H)+.
Example 581
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(l -methyl- lH-pyrazol-4-yl)-l,3-dihydro-2H- isoindole-2-carboxamide The title compound was prepared as described in Example 280, substituting 1-methyl- 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole for lH-pyrazol-3-ylboronic acid and 5-bromo-N-(4-(2-cyclopentylacetamido)phenyl)isoindoline-2-carboxamide for 5-bromo- N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 9.69 (s, 1H), 8.27 (s, 1H), 8.14 (s, 1H), 7.88 - 7.85 (m, 1H), 7.55 - 7.40 (m, 6H), 7.36 - 7.30 (m, 1H), 4.77 - 4.69 (m, 4H), 3.86 (s, 3H), 2.31 - 2.16 (m, 3H), 1.81 - 1.68 (m, 2H), 1.68 - 1.42 (m, 4H), 1.28 - 1.12 (m, 2H); MS (ESI(+)) m/e 444 (M+H)+.
Example 582
N2-{ 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-methoxyethyl)- 1 ,3-dihydro-2H-isoindole- 2,5-dicarboxamide
The title compound was prepared as described in Example 1C, substituting 2- methoxyethanamine for 3-phenylpropan-l -amine and 2-({4- [(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-i¾ δ ppm 9.69 (s, 1H), 8.56 - 8.49 (m, 1H), 8.31 (s, 1H), 7.84 - 7.77 (m, 2H), 7.50 - 7.40 (m, 5H), 4.78 (bs, 4H), 3.50 - 3.39 (m, 4H), 3.27 (s, 3H), 2.31 - 2.18 (m, 3H), 1.81 - 1.68 (m, 2H), 1.66 - 1.43 (m, 4H), 1.26 - 1.12 (m, 2H); MS (ESI(+)) m/e 465 (M+H)+.
Example 583
N2-{4-[(cyclopentylacetyl)amino]phenyl}-N5-(2 -hydro xyethyl)-l, 3-dihydro-2H-isoindole- 2,5-dicarboxamide
The title compound was prepared as described in Example 1C, substituting 2- aminoethanol for 3-phenylpropan-l -amine and 2-({4-
[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-i¾ δ ppm 9.70 (s, 1H), 8.51 - 8.40 (m, 1H), 8.31 (s, 1H), 7.86 - 7.75 (m, 2H), 7.51 - 7.36 (m, 5H), 4.78 (bs, 4H), 4.71 (t, J = 5.6 Hz, 1H), 3.58 - 3.46 (m, 2H), 3.39 - 3.28 (m, 2H), 2.32 - 2.13 (m, 3H), 1.82 - 1.68 (m, 2H), 1.67 - 1.44 (m, 4H), 1.27 - 1.10 (m, 2H); MS (ESI(+)) m/e 451 (M+H)+.
Example 584
5-(aminomemyl)-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 276, substituting 5-cyano- N- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide for 5- cyano-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO- ) δ ppm 9.35 (bs, 1H), 7.99 (bs, 1H), 7.44 - 7.41 (m, 4H), 7.31 - 7.20 (m, 3H), 4.72 (bs, 4H), 3.81 - 3.68 (m, 2H), 2.29 - 2.25 (m, 3H), 1.80 - 1.68 (m, 2H), 1.66 - 1.48 (m, 6H), 1.29 - 1.14 (m, 2H); MS (ESI(+)) m/e 393 (M+H)+. Example 605
N-[6-(benzoylamino)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 605A
tert-butyl 6-(isoindoline-2-carboxamido)hexylcarbamate
The title compound was prepared as described in Example 344A, substituting tert- butyl 6-aminohexylcarbamate for tert-butyl 5-aminoisoindoline-2-carboxylate.
Example 605B
N-(6-aminohexyl)isoindoline-2-carboxamide
The title compound was prepared as described in Example 2D, substituting Boc- tert- butyl 6-(isoindoline-2-carboxamido)hexylcarbamate for tert-butyl 4-((4-(5-fluoroisoindoline- 2-carboxamido)benzamido)methyl)benzylcarbamate.
Example 605C
N- [6-(benzoylamino)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(6- aminohexyl)isoindoline-2-carboxamide for 3-phenylpropan-l -amine and benzoic acid for 4- (isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-i¾ δ ppm 8.42 (t, 7=5.35 Hz, 1 H) 7.76 - 7.90 (m, 2 H) 7.36 - 7.58 (m, 3 H) 7.20 - 7.36 (m, 4 H) 6.28 (t, 7=5.55 Hz, 1 H) 4.57 (s, 4 H) 3.21 - 3.30 (m, 2 H) 3.07 (q, 7=6.74 Hz, 2 H) 1.24 - 1.66 (m, 8 H); (ESI(+)) m/e 366 (M+H)+.
Table 10.
The following Examples were prepared as described in Example 1C, substituting N- (6-aminohexyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and the appropriate carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic
Figure imgf000811_0001
carboxamide (s, 4 H), 7.24 - 7.33 (m, 4 H)
I N-{6- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, [(cyclopentylcarbonyl)a Temp=90°C) δ ppm 1.25 - 1.35 (m, 5 H), 1.38 - 1.55 mino]hexyl} -l,3- (m, 6 H), 1.56 - 1.67 (m, 4 H), 1.68 - 1.81 (m, 2 H), dihydro-2H-isoindole-2- 3.00 - 3.13 (m, 4 H), 4.59 (s, 4 H), 7.20 - 7.37 (m, 4 carboxamide H)
658 I I N-{6-[(2- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, hydroxybenzoyl)amino] Temp=90°C) δ ppm 1.32 - 1.42 (m, 4 H), 1.45 - 1.53 hexyl } - 1 ,3-dihydro-2H- (m, 2 H), 1.53 - 1.63 (m, 2 H), 3.11 (t, 2 H), 3.31 (t, isoindole-2- 7=7.02 Hz, 2 H), 4.58 (s, 4 H), 6.83 - 6.90 (m, 2 H), carboxamide 7.23 - 7.32 (m, 4 H), 7.34 - 7.40 (m, 1 H), 7.78 (dd,
7=7.78, 1.68 Hz, 1 H)
I N-{6-[(3- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, hydroxybenzoyl)amino Temp=90°C) δ ρριη 1.28 - 1.41 (m, 4 H), 1.42 - 1.61 hexyl } - 1 ,3-dihydro-2H (m, 4 H), 3.08 - 3.15 (m, 2 H), 3.22 - 3.25 (m, 2 H), isoindole-2- 4.59 (s, 4 H), 6.86 - 6.93 (m, 1 H), 7.17 - 7.34 (m, 7 carboxamide H)
660 I I N-{6-[(4- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, hydroxybenzoyl)amino] Temp=90°C) δ ppm 1.30 - 1.38 (m, 4 H), 1.44 - 1.60 hexyl } - 1 ,3-dihydro-2H- (m, 4 H), 3.09 - 3.13 (m, 2 H), 3.20 - 3.25 (m, 2 H), isoindole-2- 4.59 (s, 4 H), 6.75 - 6.83 (m, 2 H), 7.23 - 7.32 (m, 4 carboxamide H), 7.65 - 7.71 (m, 2 H)
661 I I N-{6-[(2- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, methoxybenzoyl) amino] Temp=90°C) δ ppm 1.29 - 1.43 (m, 4 H), 1.45 - 1.61 hexyl } - 1 ,3-dihydro-2H- (m, 4 H), 3.08 - 3.15 (m, 2 H), 3.30 (t, 7=7.02 Hz, 2 isoindole-2- H), 3.89 (s, 3 H), 4.58 (s, 4 H), 6.99 - 7.04 (m, 1 H), carboxamide 7.10 (d, 7=8.24 Hz, 1 H), 7.24 - 7.32 (m, 4 H), 7.41 - 7.47 (m, 1 H), 7.74 (dd, 7=7.63, 1.83 Hz, 1 H)
662 I I N-{6-[(3- ¾ NMR (400 MHz, DMSO-d6 Deuterium Oxide, methoxybenzoyl) amino] Temp=90°C) δ ppm 1.30 - 1.41 (m, 4 H), 1.44 - 1.62 hexyl } - 1 ,3-dihydro-2H- (m, 4 H), 3.09 - 3.14 (m, 2 H), 3.26 - 3.31 (m, 2 H), isoindole-2- 3.80 (s, 3 H), 4.58 (s, 4 H), 7.03 - 7.07 (m, 1 H), 7.24 carboxamide 7.41 (m, 7 H)
663 I I N-{6-[(4- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, methoxybenzoyl) amino] Temp=90°C) δ ppm 1.31 - 1.39 (m, 4 H), 1.49 (s, 4 hexyl } - 1 ,3-dihydro-2H- H), 3.11 (t, 7=7.02 Hz, 2 H), 3.26 - 3.28 (m, 2 H), 3.80 isoindole-2- (s, 3 H), 4.58 (s, 4 H), 6.92 - 6.97 (m, 2 H), 7.24 - 7.32 carboxamide (m, 4 H), 7.75 - 7.80 (m, 2 H)
664 I I N-{6-[(2- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, fluorobenzoyl)amino]he Temp=90°C) δ ppm 1.27 - 1.42 (m, 4 H), 1.43 - 1.64 xyl } - 1 ,3-dihydro-2H- (m, 4 H), 3.11 (t, 2 H), 3.28 (t, 7=7.02 Hz, 2 H), 4.58 isoindole-2- (s, 4 H), 7.17 - 7.33 (m, 6 H), 7.45 - 7.52 (m, 1 H), carboxamide 7.57 - 7.63 (m, 1 H)
665 I I N-{6-[(3- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, fluorobenzoyl)amino]he Temp=90°C) δ ppm 1.32 - 1.41 (m, 4 H), 1.44 - 1.61 xyl } - 1 ,3-dihydro-2H- (m, 4 H), 3.11 (t, 2 H), 3.28 (t, 7=7.02 Hz, 2 H), 4.58 isoindole-2- (s, 4 H), 7.24 - 7.33 (m, 5 H), 7.44 - 7.51 (m, 1 H), carboxamide 7.55 - 7.60 (m, 1 H), 7.65 (d, 7=8.24 Hz, 1 H)
666 I I N-{6-[(4- ¾ NMR (400 MHz, DMSO-<¼/Deuterium Oxide, fluorobenzoyl)amino]he Temp=90°C) δ ppm 1.31 - 1.38 (m, 4 H), 1.44 - 1.61 xyl } - 1 ,3-dihydro-2H- (m, 4 H), 3.11 (t, 7=7.02 Hz, 2 H), 3.26 (t, 7=7.02 Hz, isoindole-2- 2 H), 4.58 (s, 4 H), 7.16 - 7.31 (m, 6 H), 7.84 - 7.89 carboxamide (m, 2 H)
Figure imgf000813_0001
Figure imgf000814_0001
, - y ro- - . , , . m, , . m, isoindole-2- carboxamide
693 4-cyano-N- { 6-[(pyridin- ¾ NMR (400 MHz, DMSO-d6_D20, Temp=90°C) δ (ESI(+))
3- 8.99 (m, 1H), 8.71 (dd, 7 = 5.0, 1.6, 1H), 8.28 (ddd, 7 m/e 392 ylcarbonyl)amino]hexyl = 8.0, 2.3, 1.6, 1H), 7.67 (m, 2H), 7.59 (ddd, 7 = 7.9, (M+H)+ }-l,3-dihydro-2H- 5.0, 0.9, 1H), 7.48 (t, 7 = 7.7, 1H), 4.75 (d, 7 = 2.2,
isoindole-2- 2H), 4.67 (m, 2H), 3.12 (t, 7 = 7.0, 2H), 1.56 (m, 5H), carboxamide 1.37 (m, 5H)
694 5-methyl-N-{6- ¾ NMR (400 MHz, DMSO-d6_D20, Temp=90°C) δ (ESI(+))
[(pyridin-3- 9.01 (m, 1H), 8.73 (dd, 7 = 5.0, 1.6, 1H), 8.32 (ddd, 7 m/e 381 ylcarbonyl)amino]hexyl = 7.9, 2.2, 1.6, 1H), 7.62 (ddd, 7 = 8.0, 5.0, 0.9, 1H), (M+H)+ }-l,3-dihydro-2H- 7.17 (d, 7 = 7.7, 1H), 7.08 (d, 7 = 7.8, 2H), 4.54 (bs, isoindole-2- 4H), 3.11 (t, 7 = 7.0, 2H), 2.31 (s, 3H), 1.56 (m, 5H), carboxamide 1.37 (m, 5H)
695 4-chloro-N-{6- ¾ NMR (400 MHz, DMSO-d6_D20, Temp=90°C) δ (ESI(+))
[(pyridin-3- 9.00 (dd, 7 = 2.2, 0.8, 1H), 8.71 (dd, 7 = 5.0, 1.6, 1H), m/e 401 ylcarbonyl)amino]hexyl 8.29 (ddd, 7 = 8.0, 2.2, 1.7, 1H), 7.60 (m, 1H), 7.30 (M+H)+ }-l,3-dihydro-2H- (m, 3H), 4.63 (m, 4H), 3.32 (m, 2H), 3.12 (m, 2H),
isoindole-2- 1.54 (m, 5H), 1.36 (m, 5H)
carboxamide
696 5-cyano-N-{6-[(pyridin- ¾ NMR (400 MHz, DMSO-d6_D20, Temp=90°C) δ (ESI(+))
3- 8.98 (d, 7 = 1.7, 1H), 8.70 (dd, 7 = 4.9, 1.6, 1H), 8.24 m/e 392 ylcarbonyl)amino]hexyl (m, 1H), 7.68 (m, 2H), 7.54 (m, 2H), 4.65 (m, 4H), (M+H)+ }-l,3-dihydro-2H- 3.11 (m, 2H), 1.54 (m, 5H), 1.36 (m, 5H)
isoindole-2- carboxamide
697 5-chloro-N-{6- ¾ NMR (400 MHz, DMSO-d6_D20, Temp=90°C) δ (ESI(+))
[(pyridin-3- 8.99 (dd, 7 = 2.2, 0.7, 1H), 8.71 (dd, 7 = 5.0, 1.6, 1H), m/e 401 ylcarbonyl)amino]hexyl 8.27 (ddd, 7 = 8.0, 2.2, 1.7, 1H), 7.58 (m, 1H), 7.32 (M+H)+ }-l,3-dihydro-2H- (m, 3H), 4.57 (dd, 7 = 8.2, 1.9, 4H), 3.11 (m, 2H),
isoindole-2- 1.54 (m, 5H), 1.37 (m, 5H)
carboxamide
698 N-{6-[(pyridin-2- ¾ NMR (300 MHz, DMSO- ) δ ppm 8.74 (t, 7=5.76 (ESI(+)) ylcarbonyl)amino]hexyl Hz, 1 H) 8.63 (d, 7=4.75 Hz, 1 H) 7.89 - 8.12 (m, 2 H) m/e 367
}-l,3-dihydro-2H- 7.50 - 7.65 (m, 1 H) 7.19 - 7.39 (m, 4 H) 6.26 (t, (M+H)+ isoindole-2- 7=5.43 Hz, 1 H) 4.57 (s, 4 H) 3.23 - 3.35 (m, 2 H)
carboxamide 3.06 (q, 7=6.67 Hz, 2 H) 1.22 - 1.61 (m, 8 H)
Example 607
N- {4-[(cyclopentylacetyl)amino]phenyl } -5-(pyridin-4-yl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The tide compound was prepared as described in Example 280, substituting pyridin- 4-ylboronic acid for lH-pyrazol-3-ylboronic acid and 5-bromo-N-(4-(2- cyclopentylacetamido)phenyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-(¾) δ ppm 9.70 (s, 1H), 8.69 - 8.61 (m, 2H), 8.33 (s, 1H), 7.82 - 7.69 (m, 4H), 7.54 - 7.41 (m, 5H), 4.81 (bs, 4H), 2.31 - 2.15 (m, 3H), 1.82 - 1.68 (m, 2H), 1.68 - 1.43 (m, 4H), 1.26 - 1.11 (m, 2H); MS (ESI(+)) m/e 441 (M+H)+. Example 608
5-(hydroxymethyl)-N- {4- [(3-methylbutyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 272B, substituting 4- amino-N-isopentylbenzamide for 4-amino-N-propylbenzamide and isoindolin-5-ylmethanol hydrochloride for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.55 (s, 1H), 8.24 - 8.17 (m, 1H), 7.79 - 7.72 (m, 2H), 7.68 - 7.61 (m, 2H), 7.37 - 7.21 (m, 3H), 5.19 (t, J = 5.7 Hz, 1H), 4.76 (bs, 4H), 4.52 (d, 7 = 5.7 Hz, 2H), 3.30 - 3.21 (m, 2H), 1.70 - 1.54 (m, 1H), 1.47 - 1.36 (m, 2H), 0.90 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 382 (M+H)+.
Example 609
N- { 3- [( 1 -benzoylpiperidin-4-yl)oxy]propyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 609A
tert-butyl 4-(3-(isoindoline-2-carboxamido)propoxy)piperidine- 1 -carboxylate The title compound was prepared as described in Example 344A, substituting tert- butyl 4-(3-aminopropoxy)piperidine-l -carboxylate for tert-butyl 5-aminoisoindoline-2- carboxylate.
Example 609B
N-(3-(piperidin-4-yloxy)propyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl
4-(3-(isoindoline-2-carboxarnido)propoxy)piperidine-l-carboxylate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxarrddo)benzamido)methyl)benzylcarbamate.
Example 609C
N- { 3- [( 1 -benzoylpiperidin-4-yl)oxy]propyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(3-(piperidin-4-yloxy)propyl)isoindoline-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.21 - 7.50 (m, 9 H) 6.27 (t, 7=5.43 Hz, 1 H) 4.57 (s, 4 H) 3.40 - 3.58 (m, 6 H) 3.07 - 3.21 (m, 2 H) 1.74 - 1.93 (br m, 2 H) 1.62 - 1.75 (m, 2 H) 1.44 (br m, 2 H); MS (ESI(+)) m/e 408 (M+H)+.
Example 610
N-(3-{ [l-(pyridin-3-ylcarbonyl)piperidin-4-yl]oxy}propyl)-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting nicotinoyl chloride for acetyl chloride and N-(3-(piperidin-4-yloxy)propyl)isoindoline-2- carboxamide for 5-arrdno-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 8.51 - 8.70 (m, 2 H) 7.75 - 7.88 (m, 1 H) 7.46 (dd, 7=7.73, 4.96 Hz, 1 H) 7.20 - 7.38 (m, 3 H) 6.28 (t, 7=5.35 Hz, 1 H) 4.57 (s, 4 H) 3.83 - 4.01 (m, 1 H) 3.40 - 3.63 (m, 6 H) 3.16 (q, 7=6.35 Hz, 2 H) 1.35 - 1.95 (m, 7 H); MS (ESI(+)) m/e 409 (M+H)+.
Table 11.
The following Examples were essentially prepared as described in Example 1C, substituting N-(6-(l,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl)isoindoline-2-carboxamide for 3-phenylpropan-l-amine and the corresponding carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid.
Figure imgf000817_0001
2-carboxamide = 7.7 Hz, 1H), 2.24 (s, 3H), 2.98 (m, 2H)
715 N-{ l'-[(U- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ ppm (ESI(+)) dioxidotetrahydrothiop 8.70 (d, J = 2.6 Hz, 1H), 8.35 (s, 1H), 7.96 (dd, J = m/e 467 hen-3-yl)carbonyl] - 8.6, 2.6 Hz, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.38 - (M+H)+ l',2',3',6'-tetrahydro- 7.27 (m, 4H), 6.55 (m, 1H), 4.79 (s, 4H), 4.21 (m,
2,4'-bipyridin-5-yl } - 2H), 3.79 - 3.65 (m, 3H), 3.36 - 3.13 (m, 3H), 3.08 l,3-dihydro-2H- (m, 1H), 2.63 (m, 2H), 2.37 (m, 1H), 2.14 (m, 1H) isoindole-2- carboxamide
758 N-[l'-(2-hydroxy-2- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) methylpropanoyl)- 8.69 (d, J = 2.6 Hz, 1H), 8.34 (bs, 1H), 7.95 (dd, J = m/e 407 l',2',3',6'-tetrahydro- 8.6, 2.6 Hz, 1H), 7.43 (d, J = 8.6 Hz, 1H), 7.38 - (M+H)+
2,4'-bipyridin-5-yi]- 7.26 (m, 4H), 6.55 (m, 1H), 5.09 (s, 1H), 4.79 (s,
l,3-dihydro-2H- 4H), 4.32 (m, 2H), 3.93 (t, J = 5.7 Hz, 2H), 2.60 (m, isoindole-2- 2H), 1.37 (s, 6H)
carboxamide
800 N-[l'-(morpholin-4- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) ylacetyl)-l ',2',3',6'- 8.70 (d, J = 2.6 Hz, 1H), 8.34 (s, 1H), 7.95 (dd, 7 = m/e 448 tetrahydro-2,4'- 8.6, 2.6 Hz, 1H), 7.44 (d, J = 8.6 Hz, 1H), 7.38 - (M+H)+ bipyridin-5-yl]- l,3- 7.27 (m, 4H), 6.54 (m, 1H), 4.79 (s, 4H), 4.20 (m, dihydro-2H-isoindole- 2H), 3.71 (t, J = 5.2 Hz, 2H), 3.58 (m, 4H), 3.21 (s,
2-carboxamide 2H), 2.48 (m, 2H), 2.45 (m, 4H)
1466 N-(4-{ l-[(3R)- - ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ (ESI(+)) tetrahydrofuran-3- ppm 8.13 (s, 1H), 7.54 (m, 2H), 7.31 (m, 6H), 6.07 m/e 418 ylcarbonyl] - 1 ,2,3,6 - (m, 1H), 4.77 (s, 4H), 4.14 (m, 2H), 3.91 (t, J = 8.1 (M+H)+ tetrahydropyridin-4- Hz, 1H), 3.77 - 3.67 (m, 5H), 3.38 (m, 1H), 2.50 (m, yl}phenyl)-l,3- 2H), 2.02 (m, 2H)
dihydro-2H-isoindole-
2-carboxamide
1467 N-(4-{ l-[(3S)- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) tetrahydrofuran-3- 8.12 (s, 1H), 7.54 (m, 2H), 7.31 (m, 6H), 6.07 (m, m/e 418 ylcarbonyl] - 1 ,2,3,6 - 1H), 4.77 (s, 4H), 4.14 (m, 2H), 3.91 (t, J = 8.1 Hz, (M+H)+ tetrahydropyridin-4- 1H), 3.77 - 3.67 (m, 5H), 3.38 (m, 1H), 2.50 (m,
yl}phenyl)-l,3- 2H), 2.05 (m, 2H)
dihydro-2H-isoindole-
2-carboxamide
1468 N-(4-{ l-[(l,l- ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm (ESI(+)) dioxidotetrahydro-2H- 8.13 (s, 1H), 7.54 (m, 2H), 7.31 (m, 6H), 6.07 (m, m/e 480 thiopyran-4- 1H), 4.77 (s, 4H), 4.15 (m, 2H), 3.71 (t, J = 5.7 Hz, (M+H)+ yl)carbonyl]-l,2,3,6- 2H), 3.25-3.02 (m, 5H), 2.50 (m, 2H), 2.07 (m, 4H) tetrahydropyridin-4- yl}phenyl)-l,3- dihydro-2H-isoindole-
2-carboxamide
Example 611
N-(6-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}pyridazin-3-yl)- l,3-dihydro-2H- isoindole-2-carboxamide
Example 611 A
methyl 6-aminopyridazine-3-carboxylate
To a solution of 6-chloropyridazin-3 -amine (32 g, 248 mmol), Et3N (75 mL, 744 mmol) in MeOH (500 mL), Pd(dppf)Cl2 (12 g, 16.4 mmol) was added and the mixture was heated at 60 °C overnight under CO atmosphere at 50 psi. After cooling to room temperature, the reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was washed with MeOH and the precipitate was dried by high vacuum to give the title compound as a solid.
Example 61 IB
methyl 6-isocyanatopyridazine-3-carboxylate
To the solution of methyl 6-aminopyridazine-3-carboxylate (14 g, 91.5 mmol) in anhydrous toluene (700 mL) was added Et3N (11.1, 109.8 mmol). A solution of triphosgene (27.2 g, 91.5 mmol) in anhydrous toluene was added slowly at 0 °C. The reaction mixture was stirred for 2 hrs at room temperature and then heated at 90 °C for 5 hrs. After cooling to room temperature, toluene and water were added to the mixture, the mixture was separated and the organic layer was dried over anhydrous Na2S04, concentrated under reduced pressure to give the title compound as a solid.
Example 611C
methyl 6-(isoindoline-2-carboxamido)pyridazine-3-carboxylate
To a solution of methyl 6-isocyanatopyridazine-3-carboxylate (5.26 g, 29.4 mmol) in THF (100 mL), a solution of isoindoline (5.24 g, 4.41 mmol) in THF (50 mL) was added at 0 °C. The reaction mixture was stirred overnight at room temperature. The reaction mixture was filtered and the precipitate was washed with cold EtOAc and dried in high vacuum to give the title compound as a solid.
Example 61 ID
6-(isoindoline-2-carboxamido)pyridazine-3-carboxylic acid
To a solution of methyl 6-(isoindoline-2-carboxamido)pyridazine-3-carboxylate (3.7 g, 12.4 mmol) in MeOH (40 mL) and THF (40 mL), a solution of LiOH (0.7 g, 29.2 mmol) in water (10 mL) was added at room temperature. The reaction mixture was stirred overnight at room temperature. The reaction mixture was poured into water (100 mL), extracted with EtOAc (2 x 50 mL) and the aqueous layer was acidified by addition of 2 N HC1 to pH 3 to give a precipitate. The precipitate was washed with water and dried in high vacuum to give the title compound.
Example 61 IE
N-(6-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}pyridazin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting (S)- (tetrahydrofuran-3-yl)methamine for 3-phenylpropan-l-amine and 6-(isoindoline-2- carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾
NMR (300 MHz, DMSO-d6) δ 9.94 (s, 1H), 9.12 (t, J = 6.1 Hz, 1H), 8.31 (d, 7 = 9.3 Hz, 1H), 8.11 (d, J = 9.3 Hz, 1H), 7.41 - 7.28 (m, 4H), 4.89 (s, 4H), 3.80 - 3.55 (m, 3H), 3.50 (dd, J = 8.5, 5.2 Hz, 1H), 3.37 - 3.31 (m, 2H), 2.63 - 2.51 (m, 1H), 2.01 - 1.85 (m, 1H), 1.71 - 1.55 (m, 1H); MS (ESI(+)) m/e 368 (M+H)+.
Example 612
N- { 6- [(cyclopentylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting
cyclopentylmethamine for 3-phenylpropan-l-amine and 6-(isoindoline-2- carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 9.97 (s, 1H), 9.00 (t, 7 = 6.1 Hz, 1H), 8.31 (d, 7 = 9.3 Hz, 1H), 8.11 (d, 7 = 9.3 Hz, 1H), 7.41 - 7.28 (m, 4H), 5.13 - 4.72 (m, 4H), 3.31 - 3.16 (m, 2H), 2.22 (p, 7 = 7.3 Hz, 1H), 1.70 - 1.45 (m, 6H), 1.38 - 1.20 (m, 2H); MS (ESI(+)) m/e 366
(M+H)+.Example 616
5-(hydroxymemyl)-N-(4-phenylbutyl)-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1A, substituting (4- isocyanatobutyl)benzene for methyl 4-isocyanatobenzoate and isoindolin-5-ylmethanol hydrochloride for isoindoline. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 7.32 - 7.12 (m, 8H), 6.32 - 6.24 (m, 1H), 5.16 (t, 7 = 5.6 Hz, 1H), 4.54 (bs, 4H), 4.49 (d, 7 = 5.7 Hz, 2H), 3.14 - 3.05 (m, 2H), 2.64 - 2.54 (m, 2H), 1.63 - 1.39 (m, 4H); MS (ESI(+)) m/e 325 (M+H)+.
Example 617
5-(hydroxymethyl)-N-[l-(3-methylbutyl)-lH-pyrazol-4-yl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 272B, substituting 1- isopentyl-lH-pyrazol-4-amine dihydrochloride for 4-amino-N-propylbenzamide and isoindolin-5-ylmethanol hydrochloride for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 8.39 (s, 1H), 7.73 (s, 1H), 7.39 (s, 1H), 7.34 - 7.18 (m, 3H), 5.19 (t, 7 = 5.6 Hz, 1H), 4.67 (bs, 4H), 4.51 (d, 7 = 5.5 Hz, 2H), 4.04 (t, 7 = 7.1 Hz, 2H), 1.71 - 1.55 (m, 2H), 1.55 - 1.33 (m, 1H), 0.89 (d, 7 = 6.5 Hz, 6H); MS (ESI(+)) m/e 329 (M+H)+.
Example 618
N-{5-[(3-methylbutyl)carbamoyl]pyrazin-2-yl}-l,3-dihydro-2H-isoindole-2-carboxamide
Example 618A
ethyl 5-(isoindoline-2-carboxamido)pyrazine-2-carboxylate The title compound was prepared as described in Example 344A, substituting ethyl 5- aminopyrazine-2-carboxylate for tert-butyl 5-aminoisoindoline-2-carboxylate.
Example 618B
5-(isoindoline-2-carboxamido)pyrazine-2-carboxylic acid The title compound was prepared as described in Example IB, substituting ethyl 5- (isoindoline-2-carboxamido)pyrazine-2-carboxylate for methyl 4-(isoindoline-2- carboxamido)benzoate.
Example 618C
N- { 5- [(3-methylbutyl)carbamoyl]pyrazin-2-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting 3- methylbutan-1 -amine for 3-phenylpropan-l -amine and 5-(isoindoline-2- carboxamido)pyrazine-2-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- , Temp=90 °C) δ ppm 9.34 (bs, 1H), 9.17 (d, J = 1.4 Hz, 1H), 8.82 (d, J = 1.4 Hz, 1H), 8.30 - 8.23 (m, 1H), 7.36 - 7.26 (m, 4H), 4.86 (bs, 4H), 3.37 - 3.30 (m, 2H), 1.69 - 1.58 (m, 1H), 1.50 - 1.44 (m, 2H), 0.92 (d, J = 6.5 Hz, 6H); MS (ESI(+)) m/e 354 (M+H)+.
Example 621
N-(4-{(lE)-3-[benzyl(methyl)amino]prop-l-en-l-yl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide
Example 621 A
(E)-N-benzyl-N-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)prop-2-en-l -amine
In a 4 mL vial were mixed (E)-2-(3-chloroprop-l-enyl)-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (0.195 ml, 0.988 mmol) and potassium carbonate (273 mg, 1.975 mmol) in anhydrous acetonitrile (2 ml). Benzylmethylamine (0.166 ml, 1.284 mmol) was added to this mixture, and the reaction was stirred vigorously overnight at room temperature. The reaction was diluted with ethyl acetate and washed with water and brine. The organic layer was dried with sodium sulfate, decanted, and concentrated to provide the title compound.
Example 62 IB
N-(4-{(lE)-3-[benzyl(methyl)amino]prop-l-en-l-yl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 280, substituting (E)-N- benzyl-N-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)prop-2-en-l-amine for 1H- pyrazol-3-ylboronic acid and N-(4-bromophenyl)isoindoline-2-carboxamide for 5-bromo-N- (4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, DMSO-fif6, Temp=90°C) δ ppm 8.12 (s, 1H), 7.52 (m, 2H), 7.37 - 7.18 (m, 11H), 6.48 (d, J = 15.8 Hz, 1H), 6.18 (dt, J = 15.8, 6.5 Hz, 1H), 4.77 (s, 4H), 3.53 (s, 2H), 3.15 (dd, 7 = 6.5, 1.4 Hz, 2H), 2.18 (s, 3H); MS (ESI(+)) m/e 398 (M+H)+.
Example 622
N-[4-(4-phenoxypiperidin-l-yl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxamide Example 622A
1 - (4 -nitrophenyl) -4 -pheno yp iperidine
A solution of l-fluoro-4-nitrobenzene (0.15 g, 1.063 mmol) and 4-phenoxypiperidine hydrochloride (0.250 g, 1.169 mmol) in dimethylformamide (2.126 ml) was treated with potassium carbonate (0.367 g, 2.66 mmol). The suspension was stirred at ambient temperature 2 hours, at 55°C for 4 hours and at ambient temperature for 16 hours. The reaction was poured into water and the suspension was filtered and vacuum dried to provide the title compound.
Example 622B
4-(4-phenoxypiperidin- 1 -yl)aniline
The title compound was prepared as described in Example 272A, substituting l-(4- nitrophenyl)-4-phenoxypiperidine for 4-nitro-N-propylbenzamide.
Example 622C
N-[4-(4-phenoxypiperidin-l-yl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxarnide The title compound was prepared as described in Example 272B, substituting 4-(4- phenoxypiperidin-l-yl) aniline for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 8.11 (s, 1H), 7.42 - 7.24 (m, 8H), 7.02 - 6.86 (m, 5H), 4.74 (bs, 4H), 4.59 - 4.47 (m, 1H), 3.49 - 3.39 (m, 2H), 3.03 - 2.91 (m, 2H), 2.11 - 1.98 (m, 2H), 1.81 - 1.66 (m, 2H); MS (ESI(+)) m/e 414 (M+H)+.
Example 623
N-[4-(3-phenoxyazetidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 622, substituting 3- phenoxyazetidine for 4-phenoxypiperidine hydrochloride in Example 622A. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.06 (s, 1H), 7.44 - 7.25 (m, 8H), 7.03 - 6.93 (m, 1H), 6.92 - 6.85 (m, 2H), 6.47 - 6.40 (m, 2H), 5.19 - 5.08 (m, 1H), 4.73 (bs, 4H), 4.32 - 4.23 (m, 2H), 3.69 (dd, J = 8.2, 4.2 Hz, 2H); MS (ESI(+)) m/e 386 (M+H)+.
Example 624
N-(4- { [benzyl(methyl) amino] methyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide A suspension of isoindoline (0.1 g, 0.839 mmol) and N-ethyl-N-isopropylpropan-2- amine (0.219 ml, 1.259 mmol) in acetonitrile (2.80 ml) was treated with N-methylpyrrolidine (2.80 ml). The solution was cooled to 0°C and l-(chloromethyl)-4-isocyanatobenzene (0.155 g, 0.923 mmol) was added. After stirring for 2 hours at 0°C, the reaction was treated with a solution of N-methyl-l-phenylmethanamine (0.102 g, 0.839 mmol) in 0.5 mL acetonitrile. The reaction was stirred at 0°C for 5 minutes and at ambient temperture for 30 minutes. The reaction was treated with water and the mixture was stirred for 4 hours. The suspension was filtered and the solid collected was washed with water and dried under vacuum to provide the title compound. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.31 (s, 1H), 7.56 - 7.49 (m, 2H), 7.40 - 7.28 (m, 8H), 7.27 - 7.19 (m, 3H), 4.76 (bs, 4H), 3.47 (s, 2H), 3.43 (s, 2H), 2.06 (s, 3H); MS (ESI(+)) m/e 372 (M+H)+.
Example 625
5-fluoro-N-(4- { [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 410, substituing 5-fluoro- N-(4- { [tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide for N-(4-{ [tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.39 (t, J = 5.7 Hz, 1H), 7.81 - 7.73 (m, 2H), 7.69 - 7.62 (m, 2H), 7.40 (dd, J = 8.4, 5.2 Hz, 1H), 7.24 (dd, J = 9.1, 2.5 Hz, 1H), 7.15 (td, J = 8.9, 2.5 Hz, 1H), 4.80 - 4.72 (m, 4H), 3.80 - 3.68 (m, 1H), 3.68 - 3.56 (m, 2H), 3.47 (dd, 7 = 8.5, 5.2 Hz, 2H), 3.21 (dt, 7 = 13.3, 5.9 Hz, 2H), 2.01 - 1.86 (m, 1H), 1.67 - 1.53 (m, 1H); MS (ESI(+)) m/e 384 (M+H)+.
Example 626
5-fluoro-N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 411, substituing 5-fluoro- N-(4- { [tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide for N-(4- { [tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.39 (t, 7 = 5.7 Hz, 1H), 7.80 - 7.73 (m, 2H), 7.69 - 7.62 (m, 2H), 7.40 (dd, 7 = 8.4, 5.2 Hz, 1H), 7.24 (dd, 7 = 9.1, 2.5 Hz, 1H), 7.15 (td, 7 = 8.9, 2.5 Hz, 1H), 4.80 - 4.73 (m, 4H), 3.80 - 3.56 (m, 3H), 3.47 (dd, 7 = 8.5, 5.2 Hz, 1H), 3.24 - 3.13 (m, 2H), 2.01 - 1.86 (m, 1H), 1.67 - 1.53 (m, 1H); MS (ESI(+)) m/e 384 (M+H)+.
Example 636
N-[4-(l -benzyl- lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide
Example 636A
N-(4-ethynylphenyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 1A, substituting 1-ethynyl-
4-isocyanatobenzene for methyl 4-isocyanatobenzoate.
Example 636B
N-[4-(l -benzyl- lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide A mixture of N-(4-ethynylphenyl)isoindoline-2-carboxamide (100 mg, 0.381 mmol), benzylamine (33.2 mg, 0.381 mmol), and sodium ascorbate (15 mg, 0.076 mmol) in methanol (1.9 ml) was treated with IH-imidazole-l-sulfonyl azide hydrochloride (66.0 mg, 0.381 mmol), copper(II) sulfate pentahydrate (9.52 mg, 0.038 mmol) and triethylamine (63.8 μΐ, 0.457 mmol). Additional methanol (2 mL) was added and the vial was flushed with nitrogen and stirred for 2 days. The mixture was diluted with water and the resulting suspension was filtered with water washes to provide the title compound as a white solid. ¾ NMR (300 MHz, DMSO- ) δ 8.51 (s, 1H), 8.45 (s, 1H), 7.73 (d, 7 = 8.7 Hz, 2H), 7.65 (d, 7 = 8.9 Hz, 2H), 7.49 - 7.24 (m, 9H), 5.63 (s, 2H), 4.78 (s, 4H), 1.11 - 1.00 (m, 1H); MS (ES1(+)) m/e 396 (M+H)+.
Table 12.
The following Examples were essentially prepared as described in Example 636B, substituting the appropriate amine for benzylamine.
Figure imgf000824_0001
(cyclopentylmethyl) - 1 H- (s, 1H), 7.73 (d, 7 = 8.7 Hz, IH), 7.66 (d, 7 = 8.8 m/e 388 l,2,3-triazol-4- Hz, IH), 7.41 - 7.28 (m, 4H), 4.79 (s, 2H), 4.31 (d, (M+H)+ yl]phenyl } - 1 ,3-dihydro- 7 = 7.5 Hz, IH), 3.31 (s, 2H), 2.40 (dt, 7 = 15.1, 7.4
2H-isoindole-2- Hz, IH), 1.73 - 1.47 (m, 6H), 1.36 - 1.21 (m, 2H) carboxamide
N-{4-[l-(3- ¾ NMR (300 MHz, DMSO-<¾) δ 8.46 (s, IH), 8.45 (ESI(+)) methoxypropyl)-lH- (s, IH), 7.73 (d, 7 = 8.8 Hz, 2H), 7.66 (d, 7 = 8.8 m/e 378 l,2,3-triazol-4- Hz, 2H), 7.42 - 7.26 (m, 4H), 4.79 (s, 4H), 4.43 (t, (M+H)+ yl]phenyl } - 1 ,3-dihydro- 7 = 7.1 Hz, 2H), 3.38 - 3.32 (m, IH), 3.25 (s, 3H),
2H-isoindole-2- 2.10 (p, 7 = 6.4 Hz, 2H)
carboxamide
Example 646
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide (50 mg, 0.128 mmol) and methanol (10 ml) were added to 5% Pd-C, wet (10.00 mg, 0.094 mmol) in a 50 ml pressure bottle and stirred for 16 hours at 30 psi and room temperature. The mixture was filtered through a nylon membrane and concentrated. Chromatography provided the title compound. ¾ NMR (500 MHz,
DMSO- ) δ ppm 8.60 (s, IH), 8.50 (d, 7 = 5.0 Hz, IH), 8.35 (s, IH), 7.49 - 7.40 (m, 3H), 7.13 (m, 2H), 4.79 (m, 4H), 4.56 (m, IH), 4.05 (m, IH), 3.12 (m, IH), 2.90 (m, IH), 2.71 (m, IH), 2.57 (m, IH), 1.79 (m, 2H), 1.55 - 1.30 (m, 2H), 1.02 (m, 6H); MS (ESI(+)) m/e 393 (M+H)+.
Example 647
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 646, substituting N-(4-{ 1- [(2-methoxyethoxy)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide for N-[4-( 1 -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (500 MHz, DMSO- ) δ ppm 8.27 (s, IH), 7.47 (m, 2H), 7.39 - 7.28 (m, 4H), 7.12 (m, 2H), 4.75 (bs, 4H), 4.47 (m, IH), 4.24 - 4.09 (m, 2H), 3.90 (m, IH), 3.57 (m, 2H), 3.47 (t, 7 = 4.7 Hz, 2H), 3.26 (s, 3H), 3.06 (m, IH), 2.70 (m, IH), 2.62 (m, IH), 1.77 (m, 2H), 1.57 (m, IH), 1.42 (m, IH); MS (ESI(+)) m/e 438 (M+H)+.
Example 648
N- {5-[ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]pyridin-2-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 646, substituting Ν-[Γ- (tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro-2H- isoindole-2-carboxamide for N- [4-( 1 -isobutyryl- 1 ,2,3 ,6-tetrahydropyridin-4-yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (500 MHz, DMSO-d6) δ ppm 8.81 (s, 1H), 8.16 (d, 7 = 2.4 Hz, 1H), 7.85 (d, 7 = 8.6 Hz, 1H), 7.63 (dd, 7 = 8.7, 2.4 Hz, 1H), 7.39 - 7.25 (m, 4H), 4.80 (s, 4H), 4.56 (d, 7 = 13.1 Hz, 1H), 4.08 (d, 7 = 12.3 Hz, 1H), 3.88 (m, 1H), 3.72 (m, 3H), 3.38 (m, 1H), 3.11 (m, 1H), 2.78 (dd, 7 = 11.9, 9.2 Hz, 1H), 2.63 (m, 1H), 2.03 (m, 2H), 1.80 (t, 7 = 15.4 Hz, 2H), 1.51 (m, 2H); MS (ESI(+)) m/e 421 (M+H)+.
Example 651
N-(r-isobutyryl-1^2^3^6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
Example 651 A
N-(6-chloropyridin-3-yl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide
The title compound was prepared as described in Example 1A, substituting 2-chloro-
5-isocyanatopyridine for methyl 4-isocyanatobenzoate and 2,3-dihydro-lH-pyrrolo[3,4- c]pyridine for isoindoline.
Example 65 IB
tert-butyl 4-(5-(2,3-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)pyridin-2-yl)-5,6- dihydropyridine- 1 (2H)-carboxylate
The title compound was prepared as described in Example 280, substituting tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-l(2H)-carboxylate for lH-pyrazol-3-ylboronic acid and N-(6-chloropyridin-3-yl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 5-bromo-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide.
Example 651C
N-(6-(l,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide
The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(5-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)pyridin-2-yl)-5,6- dihydropyridine- l(2H)-carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate.
Example 65 ID
N-(r-isobutyryl-l',2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(6-
(l,2,3,6-tetrahydropyridin-4-yl)pyridin-3-yl)isoindoline-2-carboxamide for 3-phenylpropan- 1 -amine and isobutanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (501 MHz, DMSO- , Temp=90°C) δ ppm 8.73 (d, 7 = 2.6 Hz, 1H), 8.64 (s, 1H), 8.52 (m, 2H), 7.99 (dd, 7 = 8.6, 2.6 Hz, 1H), 7.49 (d, 7 = 8.7 Hz, 1H), 7.44 (d, 7 = 5.0 Hz, 1H), 6.60 (m, 1H), 4.88 (bs, 2H), 4.85 (d, 7 = 2.3 Hz, 2H), 4.22 (m, 2H), 3.73 (t, 7 = 5.7 Hz, 2H), 2.96 (m, 1H), 2.63 (m, 2H), 1.08 (d, 7 = 6.7 Hz, 6H); MS (ESI(+)) m/e 392 (M+H)+.
Table 13. The following Examples were essentially prepared as described in Example 1C, substituting N-(6-(l,2 ,6-tetrahydropyridin-4-yl)pyridin-3-yl)-lH-pyrrolo[3,4-c]pyridine- 2(3H)-carboxamide for 3-phenylpropan-l -amine and the corresponding carboxylic acid for 4-
(isoindoline-2-carboxamido)benzoic acid.
Figure imgf000827_0001
n-3-yl)carbonyl]- 8.48 (d, J = 5.0 Hz, 1H), 8.43 (s, 1H), 7.95
r,2',3',6'-tetrahydro-2,4'- (dd, J = 8.7, 2.6 Hz, 1H), 7.45 (d, J = 8.7 Hz,
bipyridin-5-yl } - 1 ,3- 1H), 7.39 (d, 7= 4.9 Hz, 1H), 6.55 (m, 1H),
dihydro-2H-pyrrolo[3,4- 4.82 (m, 4H), 4.21 (s, 2H), 3.85 - 3.65 (m,
c]pyridine-2- 3H), 3.35 - 3.13 (m, 3H), 3.06 (m, 1H), 2.63
carboxamide (bs, 2H), 2.37 (m, 1H), 2.13 (m, 1H)
N-[l'-(2-hydroxy-2- ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ (ESI(+)) m/e methylpropanoyl)- ppm 8.68 (s, 1H), 8.59 (s, 1H), 8.48 (d, 7 = 4.8 408 (M+H)+ r,2',3',6'-tetrahydro-2,4'- Hz, 1H), 8.41 (s, 1H), 7.94 (m, 1H), 7.43 (d, 7
bipyridin-5 -yl] - 1 , 3 - = 8.6 Hz, 1H), 7.39 (d, 7= 4.7 Hz, 1H), 6.55
dihydro-2H-pyrrolo[3,4- (m, 1H), 5.09 (s, 1H), 4.82 (m, 4H), 4.32 (bs,
c]pyridine-2- 2H), 3.92 (bs, 2H), 2.59 (bs, 2H), 1.37 (s, 6H)
carboxamide
Example 699
N-{4-[l-(pyridin-2-ylcarbonyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 278, substituting picolinoyl chloride for acetyl chloride and N-[4-(piperidin-4-yl)butyl]-l,3-dihydro-2H- isoindole-2-carboxamide for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2- carboxamide. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.56 (d, 7=4.76 Hz, 1 H) 7.83 - 7.97 (m, 1 H) 7.38 - 7.57 (m, 2 H) 7.18 - 7.40 (m, 4 H) 6.27 (t, 7=5.55 Hz, 1 H) 4.56 (s, 4 H) 4.47 (d, 7=13.09 Hz, 1 H) 3.59 (d, 7=13.88 Hz, 1 H) 3.00 - 3.16 (m, 3 H) 2.92 - 3.01 (m, 1 H) 2.68 - 2.81 (m, 1 H) 1.77 (d, 7=12.69 Hz, 1 H) 0.97 - 1.64 (m, 11 H); MS (ESI(+)) m/e 407 (M+H)+.
Example 718
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide
Example 718 A
benzyl (tetrahydrofuran-3-yl)methylcarbamate
Racemic (tetrahydrofuran-3-yl)methanamine (3.84 g, 38.0 mmol) and
diisopropylethylamine (13.26 ml, 76 mmol), were dissolved in dichloromethane (100 ml) and cooled to 0°C. The mixture was treated dropwise via an addition funnel with benzyl carbonochloridate (6.19 ml, 41.8 mmol) dissolved in 30 ml dichlormethane. After the addition the cooling bath was removed and the homogeneous solution was stirred at ambient temperature overnight. The reaction mixture was partitioned between water and ethyl acetate and the separated aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated.
Chromatography provided the title compound.
Example 718B
(S)-benzyl (tetrahydrofuran-3-yl)methylcarbamate
A racemic mixture of benzyl (tetrahydrofuran-3-yl)methylcarbamate was dissolved in tetrahydrofuran and separated by liquid chromatography with a Chiralpak IC 2.5 cm ID x 25 cm, 20 micron column, eleuting with hexane/tetrahydrofuran/isopropanol (85/10/5), to provide (R)-benzyl (tetrahydrofuran-3-yl)methylcarbamate and (S)-benzyl (tetrahydrofuran-3- yl)methylcarbamate.
Example 718C
(S)-(tetrahydrofuran-3-yl)meth an amine
(R)-Benzyl (tetrahydrofuran-3-yl)methylcarbamate (8.9 g, 37.8 mmol) and ethanol (160 ml) were added to 20% wet palladium (II) hydroxide (0.890 g, 6.34 mmol) in a 250 mL stainless steel pressure bottle and stirred for 40 minutes at 30 psi and room temperature. The mixture was filtered through a nylon filter and acidified with 4N HC1 in dioxane (5 eq). Concentration and drying provided the title compound.
Example 718D
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting (S)- (tetrahydrofuran-3-yl)methanamine for 3-phenylpropan-l -amine and 4-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)benzoic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.64 (s, 2H), 8.61 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.38 (t, J = 5.7 Hz, 1H), 7.81 - 7.74 (m, 2H), 7.69 - 7.62 (m, 2H), 7.44 (d, 7 = 5.1 Hz, 1H), 4.86 - 4.79 (m, 4H), 3.80 - 3.66 (m, 2H), 3.67 - 3.56 (m, 1H), 3.47 (dd, J = 8.5, 5.3 Hz, 1H), 3.21 (dt, J = 13.2, 5.8 Hz, 1H), 2.01 - 1.86 (m, 1H), 1.67 - 1.53 (m, 1H); MS (ESI(+)) m/e 367 (M+H)+.
Example 720
N-(7-oxo-7-{ [(3R)-tetrahydrofuran-3-ylmethyl]amino}heptyl)-l,3-dihydro-2H-isoindole-2- carboxamide
Example 720A
methyl 7-(isoindoline-2-carboxamido)heptanoate The title compound was prepared as described in Example 344A, substituting methyl 7-aminoheptanoate for tert-butyl 5-aminoisoindoline-2-carboxylate.
Example 720B
7-(isoindoline-2-carboxamido)heptanoic acid
The title compound was prepared as described in Example IB, substituting methyl 7- (isoindoline-2-carboxamido)heptanoate for methyl 4-(isoindoline-2-carboxamido)benzoate.
Example 720C
N-(7-oxo-7-{ [(3R)-tetrahydrofuran-3-ylmethyl]amino}heptyl)-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting (R)- (tetrahydrofuran-3-yl)methanamine for 3-phenylpropan-l -amine and 7-(isoindoline-2- carboxamido)heptanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 7.85 (t, 7=5.76 Hz, 1 H) 7.20 - 7.37 (m, 4 H) 6.26 (t, 7=5.59 Hz, 1 H) 4.57 (s, 4 H) 3.49 - 3.79 (m, 3 H) 3.35 (dd, 7=8.48, 5.43 Hz, 1 H) 2.94 - 3.15 (m, 4 H) 2.18 - 2.38 (m, 1 H) 2.05 (t, 7=7.29 Hz, 2 H) 1.79 - 1.98 (m, 1 H) 1.35 - 1.60 (m, 7 H) 1.17 - 1.35 (m, 2 H); MS (ESI(+)) m/e 374 (M+H)+.
Example 721
N-{7-oxo-7-[(tetrahydro-2H-pyran-4-ylmethyl)amino]heptyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting
(tetrahydro-2H-pyran-4-yl)methanamine for 3-phenylpropan-l-amine and 7-(isoindoline-2- carboxamido)heptanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- d6) δ ppm 7.76 (t, 7=5.75 Hz, 1 H) 7.20 - 7.40 (m, 4 H) 6.26 (t, 7=5.55 Hz, 1 H) 4.57 (s, 4 H) 3.82 (dd, 7=11.10, 2.78 Hz, 2 H) 3.14 - 3.29 (m, 2 H) 3.05 (q, 7=6.74 Hz, 2 H) 2.92 (t, 7=6.15 Hz, 2 H) 2.06 (t, 7=7.54 Hz, 2 H) 1.33 - 1.65 (m, 9 H) 1.19 - 1.34 (m, 2 H) 0.98 - 1.22 (m, 2 H); MS (ESI(+)) m/e 388 (M+H)+.
Example 722
N-[4-(l-benzoylpiperidin-4-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide
Example 722A
tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)butyl)piperidine-l- carboxylate
The title compound was prepared as described in Example 344, substituting tert-butyl 4-(4-aminobutyl)piperidine-l -carboxylate for tert-butyl 5-aminoisoindoline-2-carboxylate and substituting l,3-dihydro-2H-pyrrolo[3,4-c]pyridine for isoindoline in Example 344A.
Example 722B
N-(4-(piperidin-4-yl)butyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide
The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)butyl)piperidine-l -carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate.
Example 722C
N-[4-(l-benzoylpiperidin-4-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 1C, substituting N-(4- (piperidin-4-yl)butyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 3-phenylpropan-l- amine and benzoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (500 MHz, DMSO- d6, Temp=90°C) δ ppm 8.54 (s, 1 H) 8.45 (d, 7=5.04 Hz, 1 H) 7.38 - 7.46 (m, 3 H) 7.28 - 7.37 (m, 3 H) 6.09 (s, 1 H) 4.62 (dd, 7=9.08, 1.60 Hz, 4 H) 3.07 - 3.15 (m, 2 H) 2.79 - 2.94 (m, 2 H) 1.61 - 1.75 (m, 2 H) 1.41 - 1.58 (m, 3 H) 1.20 - 1.40 (m, 4 H) 0.99 - 1.17 (m, 2 H); MS (ESI(+)) m/e 407 (M+H)+.
Table 14.
The following Examples were essentially prepared as described in Example 722C, substituting an appropriate carboxylic acid for benzoic acid.
Figure imgf000831_0001
Figure imgf000832_0001
y ro- - . , = . z, , . t, = . , . z, pyrrolo[3,4-c]pyridine- 3H), 1.38 - 1.29 (m, 4H), 1.25 (dt, J = 13.6, 6.8 Hz,
2-carboxamide 3H), 1.03 (s, 3H)
Example 753
N-{4-[5-(moφholin-4-ylmethyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide
Example 753A
N-(4-(5-(chloromethyl)-l,2,4-oxadiazol-3-yl)phenyl)isoindoline-2-carboxamide To a 25 mL round-bottomed flask containing (Ζ)-Ν-(4-(Ν'- hydroxycarbamimidoyl)phenyl)isoindoline-2-carboxamide (1.5 g, 5.06 mmol) in acetone (5 ml)was added potassium carbonate (7.00 g, 50.6 mmol) in a single portion. The reaction mixture was cooled to 0°C and 2-chloroacetyl chloride (3.22 ml, 40.5 mmol) was added slowly. The resulting mixture was warmed to room temperature and stirred for two hours. The solvent was removed and the solid was triturated with water and then filtered with water washes. The dried solid was dissolved in DMF, heated to 100°C and stirred for two hours. Work-up with water and dichlormethane followed by chromatography provided the title compound.
Example 753B
N-{4-[5-(morpholin-4-ylmethyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide
To a 20 mL vial was added N-(4-(5-(chloromethyl)-l,2,4-oxadiazol-3- yl)phenyl)isoindoline-2-carboxamide (50 mg, 0.141 mmol) and morpholine (36.8 mg, 0.423 mmol) in DMF (470 μΐ). The mixture was heated to 50°C for 30 minutes, cooled, and diluted with 2 mL methanol. Chromatography provided the title compound. ¾ NMR (300 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.80 (d, J = 8.9 Hz, 2H), 7.35 (ddd, J = 8.8, 3.9, 2.4 Hz, 4H), 4.80 (s, 4H), 3.95 (s, 2H), 3.68 - 3.48 (m, 4H), 2.62 - 2.51 (m, 5H); MS (ESI(+)) m/e 406 (M+H)+.
Example 754
N-(4-{5-[(4-methylpiperazin-l-yl)methyl]-l,2,4-oxadiazol-3-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 753B, substituting 1- methylpiperazine for morpholine. ¾ NMR (300 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.91 (d, J = 8.8 Hz, 3H), 7.80 (d, J = 8.8 Hz, 3H), 7.45 - 7.23 (m, 5H), 4.80 (s, 5H), 3.93 (s, 2H), 2.65 - 2.51 (m, 75H), 2.34 (s, 5H), 2.15 (s, 4H); MS (ESI(+)) m/e 419 (M+H)+.
Example 755
N-[4-(5- { [(3-methylbutyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide The title compound was prepared as described in Example 753B, substituting 3- methylbutan-1 -amine for morpholine. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.68 (s, 1H), 7.91 (d, J = 8.8 Hz, 2H), 7.79 (d, 7 = 8.8 Hz, 2H), 7.35 (tdd, 7 = 8.9, 5.4, 3.4 Hz, 4H), 4.80 (s, 4H), 4.02 (s, 2H), 2.66 - 2.53 (m, 1H), 2.43 - 2.30 (m, 1H), 1.63 (dt, 7 = 13.4, 6.7 Hz, 1H), 1.32 (dd, 7 = 14.4, 7.0 Hz, 2H), 0.86 (d, 7 = 6.5 Hz, 6H) ; MS (ESI(+)) m/e 406 (M+H)+.
Example 756
N-(4- { 5- [(4-hydroxypiperidin- 1 -yl)methyl] - 1 ,2,4-oxadiazol-3-yl } phenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 753B, substituting piperidin-4-ol for morpholine. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.68 (s, 1H), 7.91 (d, 7 = 8.8 Hz, 2H), 7.79 (d, 7 = 8.8 Hz, 2H), 7.45 - 7.25 (m, 4H), 4.80 (s, 4H), 4.56 (d, 7 = 4.2 Hz, 1H), 3.91 (s, 2H), 3.45 (dd, 7 = 8.7, 4.3 Hz, 1H), 3.17 (d, 7 = 5.2 Hz, 1H), 2.76 (dd, 7 = 10.6, 5.0 Hz, 2H), 2.42 - 2.18 (m, 3H), 1.72 (d, 7 = 8.9 Hz, 2H), 1.43 (dt, 7 = 18.5, 6.4 Hz, 2H); MS (ESI(+)) m/e 420 (M+H)+.
Example 787
N-[4-(2-{benzyl[3-(morpholin-4-yl)propyl]amino}-2-oxoethyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide
Example 787 A
N-benzyl -N- ( 3 -morpholinopropyl) - 2 - (4 -nitrophenyl) acetamide The title compound was prepared as described in Example 1C, substituting N-benzyl -
3-morpholinopropan-l -amine for 3-phenylpropan-l -amine and 2-(4-nitrophenyl)acetic acid for 4-(isoindoline-2-carboxamido)benzoic acid.
Example 787B
2-(4-aminophenyl)-N-benzyl-N-(3-morpholinopropyl)acetamide The title compound was prepared as described in Example 272A, substituting N- benzyl-N-(3-morpholinopropyl)-2-(4-nitrophenyl)acetamide for 4-nitro-N-propylbenzamide.
Example 787C
N-[4-(2-{benzyl[3-(morpholin-4-yl)propyl]amino}-2-oxoethyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 272B, substituting 2-(4- aminophenyl)-N-benzyl-N- (3 -morpholinopropyl) acetamide for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ ppm 8.05 (bs, 1H), 7.47 (d, 7 = 8.5 Hz, 2H), 7.37 - 7.17 (m, 9H), 7.15 - 7.08 (m, 2H), 4.76 (s, 4H), 4.56 (bs, 2H), 3.77 - 3.55 (m, 2H), 3.56 - 3.50 (m, 4H), 3.30 (t, 7 = 7.3 Hz, 2H), 2.33 - 2.24 (m, 4H), 2.21 (t, 7 = 6.8 Hz, 2H), 1.60 (p, 7 = 7.1 Hz, 2H); MS (ESI(+)) m/e 513 (M+H)+. Example 788
N-[4-(3-{benzyl[3-(morpholin-4-yl)propyl] amino} -3-o xopropyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide
The tide compound was prepared as described in Example 787, substituting 3-(4- nitrophenyl)propanoic acid for 2-(4-nitrophenyl)acetic acid in Example 787 A. ¾ NMR (400 MHz, DMSO-<¾, Temp=90 °C) δ ppm 7.99 (bs, 1H), 7.48 - 7.39 (m, 2H), 7.37 - 7.19 (m, 7H), 7.19 - 7.13 (m, 2H), 7.13 - 7.00 (m, 2H), 4.76 (s, 4H), 4.53 (s, 2H), 3.56 - 3.45 (m, 4H), 3.31 - 3.23 (m, 2H), 2.87 - 2.78 (m, 2H), 2.72 - 2.57 (m, 2H), 2.29 - 2.22 (m, 4H), 2.20 (t, J = 6.8 Hz, 2H), 1.63 - 1.54 (m, 2H); MS (ESI(+)) m/e 527 (M+H)+.
Example 795
N- {6- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting tetrahydro-2H-pyran-4-ylmethamine for 3-phenylpropan-l -amine and 6-(isoindoline-2- carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 9.98 (s, 1H), 9.03 (t, J = 6.2 Hz, 1H), 8.31 (d, 7 = 9.3 Hz, 1H), 8.10 (d, J = 9.3 Hz, 1H), 7.41 - 7.28 (m, 4H), 5.03 - 4.67 (m, 4H), 3.89 - 3.79 (m, 2H), 3.29 - 3.11 (m, 4H), 2.01 - 1.78 (m, 1H), 1.63 - 1.53 (m, 2H), 1.30 - 1.12 (m, 2H); MS (ESI(+)) m/e 382 (M+H)+.
Example 797
N-[4-(6-bromo-2-oxoquinolin-l(2H)-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide
Example 797A
tert-butyl 4-(6-bromo-2-oxoquinolin- 1 (2H)-yl)butylcarbamate To a solution of 6-bromoquinolin-2(lH)-one (430 mg, 1.91 mmol) in tetrahydrofuran (8 ml) was added sodium bis(trimethylsilyl)amide (2.1 ml, 2.08 mmol). After 15 minutes, 4- (boc-amino)butyl bromide (403 mg, 1.6 mmol)was added. The solution was stirred for 15 hours, concentrated and purified by flash chromatography to provide the title compound.
Example 797B
1 -(4-aminobutyl)-6-bromoquinolin-2( lH)-one The title compound was prepared as described in Example 2D, substituting tert-butyl
4-(6-bromo-2-oxoquinolin-l(2H)-yl)butylcarbamate for tert-butyl 4-((4-(5-fluoroisoindoline- 2-carboxamido)benzamido)methyl)benzylcarbamate.
Example 797C
N-[4-(6-bromo-2-oxoquinolin-l(2H)-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting l-(4- aminobutyl)-6-bromoquinolin-2(lH)-one for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (400 MHz, CDC13) δ ppm 7.67 (d, 7 = 2.2 Hz, 2 H), 7.61 (d, 7 = 2.3 Hz, 1 H), 7.60 (d, 7 = 2.3 Hz, 1 H), 7.57 (d, 7 = 9.6 Hz, 2 H),
7.28 (s, 1 H), 7.24 (s, 1 H), 6.70 (d, 7 = 9.5 Hz, 2 H), 4.76 (t, 7 = 5.7 Hz, 2 H), 4.70 (s, 4 H),
4.29 (m, 2 H), 3.42 (m, 2 H), 1.79 (m, 2H), 1.69 (m, 2H); MS (ESI(+)) m/e 440.1 (M+H).
Example 798
N-{4-[6-(3-acetylphenyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 280, substituting 3- acetylphenyl boronic acid for lH-pyrazol-3-ylboronic acid and N-[4-(6-bromo-2-oxoquinolin- 1 (2H)-yl)butyl] - 1 ,3 -dihydro-2H-isoindole-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, CDC13) δ ppm 8.20 (t, 7 = 1.5 Hz, 1 H), 7.94 (d, 7 = 7.7 Hz, 1 H), 7.80 (m, 3 H), 7.75 (d, 7 = 9.5 Hz, 2 H), 7.56 (t, 7 = 7.7 Hz, 1 H), 7.49 (d, 7 = 9.4 Hz, 2 H), 7.24 (s, 1H), 6.75 (t, 7 = 9.4 Hz, 2 H), 4.82 (t, 7 = 5.4 Hz, 1 H), 4.72 (s, 4H), 4.37 (m, 2H), 3.45 (m, 2H), 2.66 (s, 3H), 1.88 (m, 2H), 1.74 (m, 2H); MS (ESI(+)) m/e 480.3 (M+H).
Example 804
5-(hydroxymethyl)-N-(3-phenylpropyl)-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting 3- phenylpropan-1 -amine for 4-amino-N-propylbenzamide and isoindolin-5-ylmethanol hydrochloride for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.30 - 7.14 (m, 8H), 6.30 (t, 7 = 5.5 Hz, 1H), 5.16 (t, 7 = 5.5 Hz, 1H), 4.55 (bs, 4H), 4.49 (d, 7 = 4.9 Hz, 2H), 3.16 - 3.05 (m, 2H), 2.64 - 2.56 (m, 2H), 1.76 (p, 7 = 7.4 Hz, 2H); MS (ESI(+)) m/e 311 (M+H)+.
Example 805
N-(2-{(4-fluorobenzyl) [4-(pyridin-3-yl)benzyl] amino }-l, 3-thiazol-5-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
Example 805A
methyl 2-(4-(pyridin-3-yl)benzylamino)thiazole-5-carboxylate In a 250 mL round-bottomed flask was added 4-(pyridin-3-yl)benzaldehyde (4 g, 21.83 mmol), methyl 2-aminothiazole-5-carboxylate (3.45 g, 21.83 mmol), and acetic acid (0.375 ml, 6.55 mmol) in toluene (109 ml). The mixture was heated at reflux under Dean- Stark conditions for 3 hours, cooled, concentrated and redissolved in methanol. The mixture was cooled to 0°C and sodium borohydride (1.322 g, 34.9 mmol) was carefully added. The mixture was warmed to room temperature and the resulting suspension was filtered with water washes to provide the title compound after drying.
Example 805B
2-((4-fluorobenzyl)(4-(pyridin-3-yl)benzyl)amino)thiazole-5-carboxylic acid In a 250 mL round-bottomed flask was added methyl 2-(4-(pyridin-3- yl)benzylamino)thiazole-5-carboxylate (3 g, 9.22 mmol) and l-(bromomethyl)-4- fluorobenzene (1.264 ml, 10.14 mmol) in dimethylformamide (46.1 ml). The mixture was cooled to 0°C, sodium hydride (0.738 g, 18.44 mmol) was added carefully; and the mixture was warmed to room temperature. After the mixture was stirred for about 30 minutes, it was found to be predominantely carboxylic acid. 1 N NaOH was added to complete the conversion; and a water work up followed by chromatography provided the title compound.
Example 805C
N-(4-fluorobenzyl)-5-isocyanato-N-(4-(pyridin-3-yl)benzyl)thiazol-2-amine To a 50 mL round-bottomed flask was added 2-((4-fluorobenzyl)(4-(pyridin-3- yl)benzyl)amino)thiazole-5-carboxylic acid (850 mg, 2.026 mmol) in dichloromethane (10.100 ml) and the solution was cooled to 0°C. Oxalyl chloride (0.266 ml, 3.04 mmol) and dimethylformamide (0.016 ml, 0.203 mmol) were added and some bubbling occured. The solution was warmed to room temperature and stirred for 1 hour. The mixture was cooled to 0°C, and trimethylsilyl azide (0.538 ml, 4.05 mmol) was added. The mixture was warmed to room temperature, stirred for 30 minutes and concentrated under vacuum. Toluene (5 ml) was added and the mixture was heated to 95°C for 2.5 hours. The toluene was removed and the resulting solid was triturated/sonicated with ether and filtered with ether washes to provide the title compound.
Example 805D
N-(2-{(4-fluorobenzyl) [4-(pyridin-3-yl)benzyl] amino }-l, 3-thiazol-5-yl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1A, substituting N-(4- fluorobenzyl)-5-isocyanato-N-(4-(pyridin-3-yl)benzyl)thiazol-2-amine for methyl 4- isocyanatobenzoate and l,3-dihydro-2H-pyrrolo[3,4-c]pyridine for isoindoline. ¾ NMR (300 MHz, DMSO-d6) δ ppm 9.27 (s, 1H), 8.99 (d, J = 2.1 Hz, 1H), 8.76 (s, 1H), 8.71 - 8.56 (m, 2H), 8.29 (d, J = 7.8 Hz, 1H), 7.81 - 7.56 (m, 5H), 7.51 - 7.27 (m, 5H), 7.27 - 7.06 (m, 2H), 6.86 (s, 1H), 4.80 (d, J = 3.6 Hz, 4H), 4.72 (d, J = 7.7 Hz, 4H); MS (ESI(+)) m/e 537 (M+H)+.
Example 806
N-[4-(2-benzyl-l,3-thiazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide
Example 806A
4-(2-benzylthiazol-4-yl)aniline
2-Bromo-l-(4-nitrophenyl)ethanone (0.5 g, 2.049 mmol) and 2- phenylethanethioamide (0.310 g, 2.049 mmol) were combined in ethanol (10 ml) in a 20 mL microwave reaction vessel and heated at 140°C for 15 minutes. The solution was transferred to a 250 mL round bottom flask where it immediately solidified. The material was diluted with an additional ethanol (10 ml) and was heated at reflux with stirring until the solids were dissolved. Water (5.0 ml, 278 mmol), and hydrochloric acid (1 ml, 12.00 mmol) were added. Iron (.625 g, 11.19 mmol) was added and the mixture was heated at reflux for 2 hours. The mixture was allowed to cool and 5 mL NH4OH was added. The material was filtered through a pad of diatomaceous earth and the pad was washed with 50 mL of ethyl acetate. The filtrate was washed with 100 mL of water and the aqueous phase was extracted with an additional 50 mL of ethyl acetate. The combined organic fractions were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The material was re-dissolved in 50 mL of ethyl acetate and filtered through a 1/4-inch pad of silica gel. The pad was washed with an additional 50 mL of ethyl acetate and the combined filtrate was concentrated to provide the title compound.
Example 806B
N-[4-(2-benzyl-l,3-thiazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting 4-(2- benzylthiazol-4-yl)aniline for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (400 MHz, CDC13) δ ppm 7.79 (d, J = 8.7 Hz, 2 H), 7.48 (d, J = 8.7 Hz, 2 H), 7.30 (s, 1H), 7.29 (d, J = 3.8 Hz, 2 H), 7.26 (m, 5H), 7.20 (d, J = 3.7 Hz, 2 H), 6.29 (s, 1H), 4.80 (s, 4 H), 4.32 (s, 2H); MS (ESI(+)) m/e 412 (M+H).
Example 807
N-(7- {benzyl[3-(morpholin-4-yl)propyl] amino } -7-oxoheptyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting N-benzyl- 3-morpholinopropan-l -amine for 3-phenylpropan-l -amine and 7-(isoindoline-2- carboxamido)heptanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.41 - 7.13 (m, 9H), 6.32 - 6.22 (m, 1H), 4.59 - 4.48 (m, 6H), 3.58 - 3.47 (m, 4H), 3.27 - 3.20 (m, 2H), 3.11 - 2.98 (m, 2H), 2.44 - 2.36 (m, 1H), 2.31 - 2.23 (m, 5H), 2.23 - 2.12 (m, 2H), 1.70 - 1.17 (m, 10H); MS (ESI(+)) m/e 507 (M+H)+.
Example 808
N- { 4- [(3-methylbutyl)sulf amoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide
Example 808A
N-isopentyl-4-nitrobenzenesulfonamide
4-Nitrobenzene-l-sulfonyl chloride (1.5 g, 6.57 mmol) was dissolved in
dichloromethane (30 ml) and cooled to 0°C followed by addition of diisopropylethylamine (2.293 ml, 13.13 mmol). 3-Methylbutan-l-amine (0.926 ml, 7.88 mmol) was dissolved in 5 ml dichloromethane and added via syringe. After the addition, the mixture was allowed to warm to room temperature for 3 hours. The solution was diluted with aqueous sodium bicarbonate and extracted twice with dichloromethane. The organics were combined, dried over magnesium sulfate, filtered and concentrated. Chromatography provided the title compound.
Example 808B
4-amino-N-isopentylbenzenesulfonamide
The title compound was prepared as described in Example 272A, substituting N- isopentyl-4-nitrobenzenesulfonamide for 4-nitro-N-propylbenzamide.
Example 808C
N- { 4- [(3-methylbutyl)sulf amoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting 4- amino-N-isopentylbenzenesulfonamide for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.75 (s, 1H), 7.82 - 7.74 (m, 2H), 7.70 - 7.64 (m, 2H), 7.41 - 7.27 (m, 5H), 4.80 (s, 4H), 2.77 - 2.67 (m, 2H), 1.64 - 1.47 (m, 1H), 1.30 - 1.19 (m, 2H), 0.79 (d, J = 6.6 Hz, 6H); MS (ESI(+)) m/e 388 (M+H)+.
Example 839
N-(5-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}pyridin-2-yl)-l,3-dihydro-2H-isoindole-
2-carboxamide
The title compound was prepared as described in Example 1C, substituting (S)-benzyl (tetrahydrofuran-3-yl)methylcarbamate for 3-phenylpropan-l -amine and 6-(isoindoline-2- carboxamido)nicotinic acid for 4-(isoindoline-2-carboxamido)benzoic acid. H NMR (500 MHz, DMSO-<¾) δ ppm 9.27 (s, 1H), 8.74 (d, J = 2.1 Hz, 1H), 8.60 (t, J = 5.7 Hz, 1H), 8.14 (dd, J = 8.8, 2.4 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.41 - 7.27 (m, 4H), 4.89 (m, 4H), 3.75 (m, 1H), 3.69 (m, 1H), 3.62 (m, 1H), 3.48 (dd, 7 = 8.5, 5.3 Hz, 1H), 3.25 (m, 2H), 2.48 (m, 1H), 1.95 (m, 1H), 1.61 (m, 1H); MS (ESI(+)) m/e 367 (M+H).
Example 871
N-[4-(4- {benzyl[3-(morpholin-4-yl)propyl] amino } -4-oxobutyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 787, substituting 3-(4- nitrophenyl)butanoic acid for 2-(4-nitrophenyl)acetic acid in Example 787A. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 8.29 - 8.21 (m, 1H), 7.51 - 7.41 (m, 2H), 7.40 - 7.13 (m, 9H), 7.11 - 6.98 (m, 2H), 4.75 (s, 4H), 4.57 - 4.47 (m, 2H), 3.60 - 3.44 (m, 4H), 3.27 - 3.13 (m, 2H), 2.60 - 2.53 (m, 1H), 2.48 - 2.34 (m, 2H), 2.33 - 2.11 (m, 7H), 1.90 - 1.71 (m, 2H), 1.66 - 1.51 (m, 2H); MS (ESI(+)) m/e 541 (M+H)+.
Example 872
N-(4-phenylbutyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1A, substituting (4- isocyanatobutyl)benzene for methyl 4-isocyanatobenzoate and l,3-dihydro-2H-pyrrolo[3,4- cjpyridine for isoindoline. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.55 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 7.38 (d, 7 = 5.1 Hz, 1H), 7.32 - 7.22 (m, 2H), 7.23 - 7.11 (m, 3H), 6.38 (t, 7 =
5.6 Hz, 1H), 4.63 - 4.57 (m, 4H), 3.10 - 3.07 (m, 2H), 2.59 (t, 7 = 7.5 Hz, 2H), 1.66 - 1.39 (m, 4H); MS (ESI(+)) m/e 296 (M+H)+.
Example 873
N-[4-(2-{benzyl[3-(moφholin-4-yl)propyl]arrdno}ethyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
Example 873A
N-benzyl-3-morpholino-N-(4-nitrophenethyl)propan-l-amine A suspension of l-(2-bromoethyl)-4-nitrobenzene (0.314 g, 1.366 mmol), N-benzyl-
3-morpholinopropan-l -amine (0.128 g, 0.546 mmol), and potassium carbonate (0.189 g, 1.366 mmol) in dimethylformamide (1.821 ml) was heated at 65°C for 20 hours. The reaction was partitioned in ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by flash chromatography to provide the title compound.
Example 873B
4-(2-(benzyl(3-morpholinopropyl)amino)ethyl)aniline The title compound was prepared as described in Example 272A, substituting N- benzyl-3-morpholino-N-(4-nitrophenethyl)propan-l -amine for 4-nitro-N-propylbenzamide.
Example 873C
N-[4-(2-{benzyl[3-(moφholin-4-yl)propyl]arnino}ethyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 272B, substituting 4-(2- (benzyl(3-morpholinopropyl)amino)ethyl)aniline for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- d6) δ ppm 8.24 (s, 1H), 7.43 (d, J = 8.5 Hz, 2H), 7.38 - 7.18 (m, 9H), 7.04 (d, 7 = 8.5 Hz, 2H), 4.75 (s, 4H), 3.60 (s, 2H), 3.54 - 3.47 (m, 4H), 2.70 - 2.54 (m, 4H), 2.48 - 2.41 (m, 2H), 2.29 - 2.16 (m, 6H), 1.62 - 1.46 (m, 2H); MS (ESI(+)) m/e 499 (M+H)+.
Example 876
5 -cyano-N- { 4- [(3-methylbutyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 272B, substituting 4- amino-N-isopentylbenzenesulfonamide for 4-amino-N-propylbenzamide and isoindoline-5- carbonitrile for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- d6) δ ppm 8.82 (s, 1H), 7.89 (s, 1H), 7.83 - 7.74 (m, 3H), 7.71 - 7.64 (m, 2H), 7.59 (d, 7 = 7.9 Hz, 1H), 7.31 (t, 7 = 5.8 Hz, 1H), 4.89 - 4.81 (m, 4H), 2.78 - 2.67 (m, 2H), 1.56 (dp, 7 = 13.3,
6.7 Hz, 1H), 1.30 - 1.19 (m, 2H), 0.78 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 413 (M+H)+. Example 877
N- {4-[(3-methylbutyl)sulfamoyl]phenyl } - 1 ,3-dmydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 272B, substituting 4- amino-N-isopentylbenzenesulfonamide for 4-amino-N-propylbenzamide and l,3-dihydro-2H- pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.82 (s, 1H), 8.62 (s, 1H), 8.51 (d, 7 = 5.0 Hz, 1H), 7.81 - 7.74 (m, 2H), 7.71 - 7.64 (m, 2H), 7.44 (d, J = 5.1 Hz, 1H), 7.32 (t, J = 5.8 Hz, 1H), 4.87 - 4.80 (m, 4H), 2.78 - 2.67 (m, 2H), 1.56 (dp, 7 = 13.3, 6.7 Hz, 1H), 1.30 - 1.13 (m, 2H), 0.78 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 389 (M+H)+.
Example 883
N-(4- { [(3-methoxybenzyl)sulfonyl] amino } phenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide
N-(4-aminophenyl)isoindoline-2-carboxamide (0.0585 g, 0.231 mmol) was suspended in dichloromethane (2 ml) followed by addition of triisopropylethylamine (0.081 ml, 0.462 mmol). (3-Methoxyphenyl)methanesulfonyl chloride (0.061 g, 0.277 mmol) was dissolved in 1 ml dichloromethane and added to the mixture via syringe slowly. The mixture was quenched with water and the separated aqueous layer was extracted with
dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated. Reverse-phase HPLC provided the title compound. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.65 (s, 1H), 8.61 (s, 1H), 8.50 (d, 7 = 5.0 Hz, 1H), 8.34 (t, 7 = 5.6 Hz, 1H), 7.80 - 7.73 (m, 2H), 7.69 - 7.61 (m, 2H), 7.44 (d, 7 = 5.0 Hz, 1H), 4.86 - 4.79 (m, 4H), 3.20 (t, 7 = 6.2 Hz, 2H), 2.46 - 2.25 (m, 3H), 2.20 (d, 7 = 7.9 Hz, 3H), 2.06 - 1.78 (m, 1H), 1.52 - 1.37 (m, 1H); MS (ESI(+)) m/e 438 (M+H)+.
Example 909
N-{4-[6-(3-acetylphenyl)-4-(3-hydroxypropyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3-dihydro-
2H-isoindole-2-carboxamide
Example 909A
6-bromo-4-(3-(tert-butyldiphenylsilyloxy)propyl)quinolin-2(lH)-one 6-Bromo-4-(3-hydroxypropyl)quinolin-2(lH)-one (4.7 g, 16.67 mmoles), imidazole (2.84 g, 41.7 mmoles) and tert-butyldiphenylsilyl chloride (5.14 mL, 20 mmoles) were stirred in dimethylformamide (60 mL) overnight at room temperature. The reaction mixture was poured into water and extracted with ethyl acetate twice. The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The crude product was purified by normal phase chromatography to provide the title compound.
Example 909B
tert-butyl 4-(6-bromo-4-(3-(tert-butyldiphenylsilyloxy)propyl)-2-oxoquinolin-l(2H)- yl)butylcarb amate The title compound was prepared as described in Example 797 A, substituting 6- bromo-4-(3-(tert-butyldiphenylsilyloxy)propyl)quinolin-2( lH)-one for 6-bromoquinolin- 2(lH)-one.
Example 909C
l-(4-aminobutyl)-6-bromo-4-(3-(tert-butyldiphenylsilyloxy)propyl)quinolin-2(lH)-one The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(6-bromo-4-(3-(tert-butyldiphenylsilyloxy)propyl)-2-oxoquinolin-l(2H)-yl)butylcarbamate for tert-butyl 4-((4-(5-fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate.
Example 909D
N-(4-(6-bromo-4-(3-hydroxypropyl)-2-oxoquinolin-l(2H)-yl)butyl)isoindoline-2- carboxamide
The title compound was prepared as described in Example 272B, substituting l-(4- aminobutyl)-6-bromo-4-(3-(tert-butyldiphenylsilyloxy)propyl)quinolin-2(lH)-one for 4- amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride followed by TBAF deprotection and work up.
Example 909E
N-{4-[6-(3-acetylphenyl)-4-(3-hydroxypropyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3-dihydro-
2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 280, substituting 3- acetylphenylboronic acid for lH-pyrazol-3-ylboronic acid and N-(4-(6-bromo-4-(3- hydroxypropyl)-2-oxoquinolin- 1 (2H)-yl)butyl)isoindoline-2-carboxamide for 5-bromo-N-(4- (propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, CDC13) δ ppm 8.24 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.87 - 7.79 (m, 2H), 7.58 (t, J = 7.7 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.28 (s, 4H), 6.71 (s, 1H), 4.74 (s, 4H), 4.41 (t, J = 7.4 Hz, 2H), 3.82 (t, J = 6.0 Hz, 2H), 3.46 (t, J = 6.7 Hz, 2H), 3.12 - 2.99 (m, 2H), 2.68 (s, 3H), 2.10 - 1.96 (m, 2H), 1.96 - 1.83 (m, 2H), 1.79 - 1.72 (m, 2H); MS (APCI(+)) m/e 538 (M+H).
Example 910
N-{4-[l-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
Example 91 OA
N-(4-(piperidin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide (2.0 g, 6.24 mmol) in 80 mL of 1 : 1 THF:methanol was added to 5% Pd on carbon (wet) (0.500 g) in a 250 mL SS pressure bottle and the mixture was stirred for 38 hours at 30 atm and 25°C. The mixture was filtered through a nylon membrane, concentrated and suspended in ether. Filtration with ether washes provided the title compound. Example 91 OB
N- { 4- [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide
The tide compound was prepared as described in Example 1C, substituting N-(4- (piperidin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 3-phenylpropan-l- amine and tetrahydrofuran-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.60 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.35 (s, 1H), 7.46 (m, 2H), 7.43 (d, 7 = 5.0 Hz, 1H), 7.14 (m, 2H), 4.79 (m, 4H), 4.54 (m, 1H), 4.07 (m, 1H), 3.88 (dt, J = 10.4, 8.1 Hz, 1H), 3.71 (m, 3H), 3.37 (m, 1H), 3.13 (m, 1H), 2.64 - 2.59 (m, 2H), 2.01 (m, 2H), 1.79 (m, 2H), 1.46 (m, 2H); MS (ESI(+)) m/e 421 (M+H).
Table 15.
The following Examples were essentially prepared as described in Example 1C, substituting N-(4-(piperidin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 3-phenylpropan-l-amine and the appropriate carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid.
Figure imgf000843_0001
carboxamide
916 N-(4-{ l-[(l,l- ¾ NMR (400 MHz, DMSO-<¾) δ ppm 8.61 (s, IH), (ESI(+)) dioxidotetrahydrothiophe 8.50 (d, 7 = 5.0 Hz, IH), 8.35 (s, IH), 7.47 (m, 2H), m/e 469 n-3- 7.43 (d, 7 = 5.0 Hz, IH), 7.14 (m, 2H), 4.79 (m, 4H), (M+H)+ yl)carbonyl]piperidin-4- 4.53 (m, IH), 4.08 (m, IH), 3.73 (m, IH), 3.26 - yl } phenyl) - 1 , 3 -dihydro- 3.04 (m, 5H), 2.69 (m, 2H), 2.35 (m, IH), 2.07 (m,
2H-pyrrolo[3,4- IH), 1.81 (m, 2H), 1.51 (m, 2H)
c]pyridine-2- carboxamide
917 N-{4-[l-(2-hydroxy-2- ¾ NMR (400 MHz, DMSO-<¾) δ ppm 8.60 (s, IH), (ESI(+)) methylpropanoyl)piperidi 8.50 (d, 7 = 5.0 Hz, IH), 8.35 (s, IH), 7.45 (m, 3H), m/e 409 n-4-yl]phenyl}-l,3- 7.13 (m, 2H), 5.38 (s, IH), 4.75 (m, 4H), 4.60 (m, (M+H)+ dihydro-2H-pyrrolo[3,4- 2H), 2.95 (m, IH), 2.80 (m, 2H), 1.77 (m, 2H), 1.48 c]pyridine-2- (m, 2H), 1.34 (s, 6H)
carboxamide
918 N-{4-[l-(morpholin-4- ¾ NMR (500 MHz, DMSO-<¾) δ ppm 8.60 (s, IH), (ESI(+)) ylacetyl)piperidin-4- 8.50 (d, 7 = 5.0 Hz, IH), 8.35 (s, IH), 7.47 (m, 2H), m/e 450 yl]phenyl } - 1 ,3-dihydro- 7.43 (d, 7 = 5.0 Hz, IH), 7.12 (m, 2H), 4.79 (m, 4H), (M+H)+
2H-pyrrolo[3,4- 4.49 (m, IH), 4.16 (m, IH), 3.58 (m, 4H), 3.26 (m, c]pyridine-2- IH), 3.06 (m, 2H), 2.71 (m, IH), 2.61 (m, IH), 2.39 carboxamide (m, 4H), 1.78 (m, 2H), 1.57 (m, IH), 1.40 (m, IH)
1279 N-(4-{ l-[(2S)- ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.60 (s, IH), (ESI(+)) tetrahydrofuran-2- 8.50 (d, 7 = 5.0 Hz, IH), 8.35 (s, IH), 7.46 (m, 2H), m/e 421 ylcarbonyl]piperidin-4- 7.43 (d, J = 5.1 Hz, IH), 7.13 (m, 2H), 4.79 (m, 4H), (M+H)+ yl } phenyl) - 1 , 3 -dihydro- 4.68 (dd, J = 7.4, 5.8 Hz, IH), 4.49 (d, J = 12.8 Hz,
2H-pyrrolo[3,4- IH), 4.10 (m, IH), 3.78 (m, 2H), 3.08 (m, IH), 2.78 c]pyridine-2- - 2.57 (m, 2H), 2.04 (m, 2H), 1.90 - 1.71 (m, 4H), carboxamide 1.61 - 1.32 (m, 2H)
1280 N-(4-{ l-[(3S)- ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.60 (s, IH), (ESI(+)) tetrahydrofuran- 3 - 8.50 (d, J = 5.0 Hz, IH), 8.35 (s, IH), 7.49 - 7.40 m/e 421 ylcarbonyl]piperidin-4- (m, 3H), 7.14 (m, 2H), 4.79 (m, 4H), 4.54 (m, IH), (M+H)+ yl } phenyl) - 1 , 3 -dihydro- 4.06 (m, IH), 3.88 (dt, J = 10.4, 8.1 Hz, IH), 3.78 -
2H-pyrrolo[3,4- 3.54 (m, 3H), 3.38 (m, IH), 3.15 (m, IH), 2.77 - c]pyridine-2- 2.56 (m, 2H), 2.04 (m, 2H), 1.79 (m, 2H), 1.59 - carboxamide 1.29 (m, 2H)
1384 N-(4-{ l-[(2R)- ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.60 (s, IH), (ESI(+)) tetrahydrofuran-2- 8.50 (d, J = 5.0 Hz, IH), 8.35 (s, IH), 7.45 (m, 3H), m/e 421 ylcarbonyl]piperidin-4- 7.13 (m, 2H), 4.79 (m, 4H), 4.68 (dd, 7 = 7.4, 5.8 Hz, (M+H)+ yl } phenyl) - 1 , 3 -dihydro- IH), 4.48 (d, J = 12.7 Hz, IH), 4.10 (d, J = 12.8 Hz,
2H-pyrrolo[3,4- IH), 3.78 (m, 2H), 3.08 (dd, 7 = 26.0, 12.3 Hz, IH), c]pyridine-2- 2.77 - 2.55 (m, 2H), 2.04 (m, 2H), 1.83 (m, 4H),
carboxamide 1.62 - 1.32 (m, 2H)
1385 N-(4-{ l-[(3R)- ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.60 (s, IH), (ESI(+)) tetrahydrofuran- 3 - 8.50 (d, 7 = 5.0 Hz, IH), 8.35 (s, IH), 7.45 (m, 3H), m/e 421 ylcarbonyl]piperidin-4- 7.14 (m, 2H), 4.79 (m, 4H), 4.54 (m, IH), 4.07 (m, (M+H)+ yl } phenyl) - 1 , 3 -dihydro- IH), 3.88 (dt, 7 = 10.4, 8.1 Hz, IH), 3.71 (m, 3H),
2H-pyrrolo[3,4- 3.37 (m, IH), 3.10 (m, IH), 2.80 - 2.55 (m, 2H),
c]pyridine-2- 2.00 (m, 2H), 1.79 (m, 2H), 1.59 - 1.33 (m, 2H)
carboxamide
Example 920
N-{5-[2-(2-chlorobenzyl)-l,3-thiazol-4-yl]-2-thienyl}-l,3-dihydro-2H-isoindole-2- carboxamide Example 920A
5-(2-(2-chlorobenzyl)thiazol-4-yl)thiophen-2-amine The title compound was prepared as described in Example 806A, substituting 2- bromo-l-(5-nittothiophen-2-yl)ethanone for 2-bromo-l-(4-nitrophenyl)ethanone and 2-(2- chlorophenyl)ethanethio amide for 2-phenylethanethioamide.
Example 920B
N-{5-[2-(2-chlorobenzyl)-l,3-thiazol-4-yl]-2-thienyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 272B, substituting 5-(2-(2- chlorobenzyl)thiazol-4-yl)thiophen-2-amine for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline -5-carboxylate hydrochloride. ¾ NMR (400 MHz, OMSO-d6) δ ppm 9.73 (s, 1 H), 7.46 - 7.55 (m, 3 H), 7.34 - 7.40 (m, 4 H), 7.28 - 7.34 (m, 2 H), 7.20 (d, J = 3.9 Hz, 1 H), 6.62 (d, J=3.9 Hz, 1 H), 4.76 (s, 4 H), 4.45 (s, 2 H); MS (ESI(+)) m/e 452.0 (M+H).
Example 921
N-[4-(4-fluorophenyl)butyl]-5-(hydroxymethyl)-l,3-dihydro-2H-isoindole-2-carboxarnide The title compound was prepared as described in Example 272B, substituting 4-(4- fluorophenyl)butylamine for 4-amino-N-propylbenzamide and isoindolin-5-ylmethanol hydrochloride for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 7.28 - 7.17 (m, 5H), 7.13 - 7.03 (m, 2H), 6.29 (t, 7 = 5.6 Hz, 1H), 5.16 (t, 7 = 5.6 Hz, 1H), 4.54 (bs, 4H), 4.49 (d, 7 = 5.5 Hz, 2H), 3.15 - 3.04 (m, 2H), 2.58 (t, 7 = 7.4 Hz, 2H), 1.63 - 1.37 (m, 4H); MS (ESI(+)) m/e 343 (M+H)+.
Example 926
N-[4-(l -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
In a 20 mL scintillation vial were mixed N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide (100 mg, 0.312 mmol), isobutyraldehyde (0.343 mmol), and sodium triacetoxyborohydride (0.43 mmol) in anhydrous dichloroethane (4 ml). The reaction mixture was stirred overnight at room temperature. This mixture was diluted with water and the resulting suspension was stirred again overnight at room temperature. The solid was filtered through a 30 mL plastic disposable Buchner funnel, and the collected solid was washed with water, dried for 2 hours, washed with ether, and dried again to provide the title compound. ¾ NMR (400 MHz, DMSO- , Temp=90 °C) δ ppm 8.58 (s, 1H), 8.47 (d, 7 = 5.0 Hz, 1H), 8.18 (m, 1H), 7.50 (m, 2H), 7.38 (d, 7 = 5.1 Hz, 1H), 7.30 (m, 2H), 6.03 (m, 1H), 4.80 (m, 4H), 3.06 (m, 2H), 2.61 (t, 7 = 5.6 Hz, 2H), 2.44 (m, 2H), 2.17 (d, 7 = 7.2 Hz, 2H), 1.82 (m, 1H), 0.89 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 377 (M+H). Example 927
N- {4-[l -(tetrahydrofuran-3-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl} - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide
The tide compound was prepared as described in Example 926, substituting tetrahydrofuran-3-carbaldehyde for isobutraldehyde. ¾ NMR (400 MHz, DMSO-fif^
Temp=90 °C) δ ppm 8.58 (s, IH), 8.48 (d, J = 5.0 Hz, IH), 8.17 (bs, IH), 7.60 (m, 2H), 7.38 (d, J = 5.0 Hz, IH), 7.30 (m, 2H), 6.05 (m, IH), 4.83 (m, 4H), 3.77 (m, 2H), 3.62 (q, J = 7.6 Hz, IH), 3.39 (m, IH), 3.10 (t, J = 3.1 Hz, 2H), 2.95 (m, IH), 2.65 (m, 2H), 2.43 (m, 2H), 2.38 (m, 2H), 1.95 (m, IH), 1.54 (m, IH); MS (ESI(+)) m/e 405 (M+H).
Example 928
N-{ 4-[l -(tetrahydro-2H-pyran-4-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 926, substituting tetrahydro-2H-pyran-4-carbaldehyde for isobutraldehyde. ¾ NMR (400 MHz, DMSO-fif^ Temp=90 °C) δ ppm 8.58 (s, IH), 8.48 (d, J = 5.0 Hz, IH), 8.17 (bs, IH), 7.50 (m, 2H), 7.38 (d, J = 5.1 Hz, IH), 7.30 (m, 2H), 6.03 (m, IH), 4.79 (m, 4H), 3.83 (m, 2H), 3.31 (td, 7 = 11.5, 2.2 Hz, 2H), 3.07 (m, 2H), 2.63 (t, J = 5.6 Hz, 2H), 2.43 (m, 2H), 2.27 (d, J = 7.1 Hz, 2H), 1.80 (m, IH), 1.64 (m, 2H), 1.17 (m, 2H); MS (ESI(+)) m/e 419 (M+H).
Example 929
N- [4-( 1 -isobutylpiperidin-4-yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 926, substituting N-(4- (piperidin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4-(l, 2,3,6- tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.60 (s, IH), 8.50 (d, J = 5.0 Hz, IH), 8.33 (s, IH), 7.43 (m, 3H), 7.13 (m, 2H), 4.79 (m, 4H), 2.41 (m, IH), 2.92 (m, 2H), 2.15 - 1.85 (m, 4H), 1.85 - 1.50 (m, 5H), 0.87 (d, J = 6.5 Hz, 6H); MS (ESI(+)) m/e 379 (M+H).
Example 930
N-{4-[l-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 926, substituting N-(4-
(piperidin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4-(l, 2,3,6- tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide and tetrahydrofuran-3-carbaldehyde for isobutraldehyde. ¾ NMR (400 MHz, DMSO-i¾ δ ppm 8.60 (s, IH), 8.50 (d, J = 5.0 Hz, IH), 8.33 (s, IH), 7.44 (m, 3H), 7.13 (m, 2H), 4.78 (m, 4H), 3.71 (m, 2H), 3.61 (q, J = 7.6 Hz, IH), 3.36 (m, 2H), 2.96 (m, 2H), 2.40 (m, IH), 2.27 (m, 2H), 96 (m, 3H), 1.72 (m, 2H), 1.66 - 1.46 (m, 3H); MS (ESI(+)) m/e 407 (M+H). Example 931
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylmethyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The tide compound was prepared as described in Example 926, substituting N-(4- (piperidin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4-(l,2,3,6- tetrahydropyridin-4-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide and tetrahydro-2H-pyran-4-carbaldehyde for isobutraldehyde. ¾ NMR (400 MHz, DMSO-<¾) δ ppm 8.60 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.33 (s, 1H), 7.44 (m, 3H), 7.12 (m, 2H), 4.79 (m, 4H), 3.83 (m, 2H), 3.27 (m, 2H), 2.92 (m, 2H), 2.40 (m, 1H), 2.14 (d, J = 7.2 Hz, 2H), 1.95 (m, 2H), 1.74 (m, 3H), 1.61 (m, 4H), 1.12 (m, 2H); MS (ESI(+)) m/e 421 (M+H).
Example 933
tert-butyl {4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)arnino]benzyl}carbamate The title compound was prepared as described in Example 272B, substituting tert- butyl 4-aminobenzylcarbamate for 4-arnino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.29 (s, 1H), 7.52 - 7.45 (m, 2H), 7.40 - 7.24 (m, 5H), 7.15 - 7.08 (m, 2H), 4.76 (bs, 4H), 4.09 - 3.99 (m, 2H), 1.39 (s, 9H); MS (ESI(+)) m/e 368 (M+H)+.
Example 934
N- { 4- [(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4-c]pyridine-2- carboxamide
Example 934A
N-(4-nitrophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide The title compound was prepared as described in Example 1A, substituting 1- isocyanato-4-nitrobenzene for methyl 4-isocyanatobenzoate and l,3-dihydro-2H-pyrrolo[3,4- c]pyridine for isoindoline.
Example 934B
N-(4-aminophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide The title compound was prepared as described in Example 272A, substituting N-(4- nitrophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 4-nitro-N-propylbenzamide.
Example 934C
N- { 4- [(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4- aminophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for 3-phenylpropan-l -amine and cyclopentylacetic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300
MHz, DMSO- ) δ ppm 9.70 (s, 1H), 8.60 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.34 (s, 1H), 7.51 - 7.40 (m, 5H), 4.82 - 4.75 (m, 4H), 2.33 - 2.17 (m, 3H), 1.81 - 1.68 (m, 2H), 1.68 - 1.43 (m, 4H), 1.27 - 1.13 (m, 2H); (ESI(+)) m/e 365 (M+H)+.
Example 936
N-[4-(5- { [(tetrahydrofuran-2-ylmethyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 753B, substituting (tetrahydrofuran-2-yl)methanamine for morpholine. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.68 (s, 1H), 7.91 (d, J = 8.7 Hz, 2H), 7.79 (d, 7 = 8.8 Hz, 2H), 7.45 - 7.20 (m, 4H), 4.80 (s, 4H), 4.08 (s, 2H), 3.95 - 3.78 (m, 1H), 3.79 - 3.66 (m, 1H), 3.66 - 3.49 (m, 1H), 2.66 (d, 7 = 5.6 Hz, 2H), 2.00 - 1.67 (m, 4H), 1.67 - 1.41 (m, 2H), 1.40 - 1.16 (m, 2H), 0.87 (dd, 7 = 9.3, 5.4 Hz, 1H); MS (ESI(+)) m/e 420 (M+H)+.
Example 937
N-(4- { 5-[(4-methoxypiperidin- 1 -yl)methyl] - 1 ,2,4-oxadiazol-3-yl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 753B, substituting 4- methoxypiperidine for morpholine. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.69 (s, 1H), 7.92 (d, 7 = 8.8 Hz, 2H), 7.80 (d, 7 = 8.8 Hz, 2H), 7.45 - 7.20 (m, 4H), 4.80 (s, 4H), 3.93 (s, 2H), 3.21 (s, 3H), 3.20 - 3.10 (m, 1H), 2.82 - 2.68 (m, 2H), 2.50 (dt, 7 = 3.6, 1.8 Hz, 2H), 2.41 - 2.24 (m, 2H), 1.92 - 1.75 (m, 2H), 1.56 - 1.37 (m, 2H); MS (ESI(+)) m/e 434 (M+H)+.
Example 938
N-[4-(5- { [4-(2-methoxyethyl)piperazin- 1 -yl]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 753B, substituting N-(2- methoxyethyl)piperazine for morpholine. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.69 (s, 1H), 7.92 (d, 7 = 8.8 Hz, 2H), 7.86 - 7.70 (m, 2H), 7.46 - 7.23 (m, 4H), 4.80 (s, 4H), 3.93 (s, 2H), 3.40 (t, 7 = 5.8 Hz, 3H), 3.21 (s, 3H), 2.55 (s, 4H), 2.45 (t, 7 = 5.8 Hz, 6H); MS (ESI(+)) m/e 463 (M+H)+.
Example 940
N-{4-[(l-pentanoylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
Example 940A
tert-butyl 4-(4-nitrophenoxy)piperidine- 1 -carboxylate 4-Hydroxy-l-piperidine-l-carboxylic acid tert-butyl ester (6.04 g, 30 mmol) was dissolved in l-fluoro-4-nitrobenzene (7.83 g, 55.5 mmol). Aqueous potassium hydroxide solution (25 percent wt, 44 mL) was added, followed by addition of tetrabutylammonium bromide (1.26 g). The reaction mixture was stirred at 35°C for 17 hours. The solid was collected by filtration and washed with water (4 x 50 mL) to provide the title compound after vacuum drying.
Example 940B
tert-butyl 4-(4-aminophenoxy)piperidine- 1 -carboxylate
The title compound was prepared as described in Example 274, substituting tert-butyl 4-(4-nitrophenoxy)piperidine-l -carboxylate for 5-nitro-N-[4-(propylcarbamoyl)phenyi]-l,3- dihydro-2H-isoindole-2-carboxamide.
Example 940C
tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenoxy)piperidine-l- carboxylate
The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(4-aminophenoxy)piperidine-l -carboxylate for 4-amino-N-propylbenzamide and 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate hydrochloride.
Example 940D
N-(4-(piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenoxy)piperidine-l- carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate.
Example 940E
N-{4-[(l-pentanoylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for 3- phenylpropan-1 -amine and pentanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.80 (s, 1H), 8.68 (d, J = 5.5 Hz, 1H), 8.36 (s, 1H), 7.77 (d, J = 5.5 Hz, 1H), 7.42 (d, J = 9.0 Hz, 1H), 6.95 - 6.87 (m, 2H), 4.87 (d, J = 6.4 Hz, 4H), 4.64 - 4.45 (m, 1H), 3.92 - 3.79 (m, 1H), 3.76 - 3.63 (m, 1H), 3.38 - 3.15 (m, 2H), 2.31 (t, 7 = 7.4 Hz, 2H), 1.96 - 1.81 (m, 2H), 1.61 - 1.41 (m, 4H), 1.38 - 1.22 (m, 2H), 0.88 (t, 7 = 7.2 Hz, 3H); MS (ESI(+)) m/e 423 (M+H)+.
Table 16.
The following Examples were essentially prepared as described in Example 940, substituting the appropriate alcohol, in place of 4-hydroxy-l-piperidine-l-carboxylic acid butyl ester in Example 940A, and the appropriate carboxylic acid in Example 940E.
Figure imgf000849_0001
dihydro-2H- 2H), 4.89 (d, 7 = 9.8 Hz, 4H), 4.57 - 4.44 (m, IH),
pyrrolo[3,4- 3.91 - 3.76 (m, IH), 3.76 - 3.57 (m, IH), 3.43 - 3.12 c]pyridine-2- (m, 2H), 2.02 (s, 3H), 1.97 - 1.77 (m, 2H), 1.68 - 1.33 carboxamide (m, 2H)
942 N-{4-[(l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+)) butyrylpiperidin-4- (d, 7 = 5.0 Hz, IH), 8.28 (s, IH), 7.43 (dd, 7 = 7.0, 1.8 m/e 409 yl)o xy] phenyl } - 1 , 3 - Hz, 3H), 6.90 (d, 7 = 9.0 Hz, 2H), 4.78 (d, 7 = 4.0 Hz, (M+H)+ dihydro-2H- 4H), 4.57 - 4.39 (m, IH), 3.95 - 3.76 (m, IH), 3.70
pyrrolo[3,4- (d, 7 = 14.0 Hz, IH), 3.23 (dd, 7 = 15.9, 6.4 Hz, IH), c]pyridine-2- 2.30 (t, 7 = 7.4 Hz, 2H), 1.90 (s, 2H), 1.51 (dq, 7 =
carboxamide 14.6, 7.3 Hz, 4H), 0.89 (t, 7 = 7.4 Hz, 3H)
943 N-(4-{ [l-(2- ¾ NMR (300 MHz, DMSO-d6) δ 8.79 (s, IH), 8.67 (ESI(+)) methylbutanoyl)pipe (d, 7 = 5.5 Hz, IH), 8.36 (s, IH), 7.76 (d, 7 = 5.5 Hz, m/e 423 ridin-4- IH), 7.42 (d, 7 = 9.0 Hz, IH), 6.91 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - IH), 4.87 (d, 7 = 5.8 Hz, 2H), 4.66 - 4.47 (m, IH),
dihydro-2H- 3.98 - 3.74 (m, 2H), 3.43 - 3.14 (m, 2H), 2.81 - 2.63 pyrrolo[3,4- (m, IH), 1.99 - 1.82 (m, 2H), 1.55 (dt, 7 = 20.8, 7.2
c]pyridine-2- Hz, IH), 1.31 (td, 7 = 13.9, 7.1 Hz, IH), 0.98 (d, 7 =
carboxamide 6.7 Hz, 3H), 0.81 (t, 7 = 7.4 Hz, IH)
944 N-(4-{ [l-(3,3,3- ¾ NMR (300 MHz, DMSO-d6) δ 8.80 (s, IH), 8.68 (ESI(+)) trifluoropropanoyl)pi (d, 7 = 5.5 Hz, IH), 8.37 (s, IH), 7.78 (d, 7 = 5.5 Hz, m/e 449 peridin-4- IH), 7.42 (d, 7 = 8.9 Hz, 2H), 6.91 (d, 7 = 8.9 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.88 (d, 7 = 7.3 Hz, 5H), 4.60 - 4.44 (m, IH),
dihydro-2H- 3.85 (dd, 7 = 14.1, 5.4 Hz, IH), 3.67 (q, 7 = 11.0 Hz, pyrrolo[3,4- 3H), 3.41 - 3.21 (m, 2H), 1.92 (dd, 7 = 16.5, 13.5 Hz, c]pyridine-2- 2H), 1.73 - 1.35 (m, 2H)
carboxamide
945 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+))
(methoxyacetyl)pipe (d, 7 = 5.0 Hz, IH), 8.28 (s, IH), 7.43 (dd, 7 = 6.9, 1.9 m/e 411 ridin-4- Hz, 3H), 6.90 (d, 7 = 9.0 Hz, 2H), 4.78 (d, 7 = 3.9 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 5H), 4.51 (dd, 7 = 7.8, 3.9 Hz, IH), 4.09 (s, 2H), 3.89 dihydro-2H- - 3.74 (m, IH), 3.62 (ddd, 7 = 8.2, 4.1, 1.1 Hz, IH), pyrrolo[3,4- 3.29 (s, 3H), 1.91 (d, 7 = 1.3 Hz, 2H), 1.69 - 1.39 (m, c]pyridine-2- 2H)
carboxamide
946 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.80 (s, IH), 8.69 (ESI(+))
(tetrahydrofuran-2- (d, 7 = 5.5 Hz, IH), 8.36 (s, IH), 7.78 (d, 7 = 5.5 Hz, m/e 437 ylcarbonyl)piperidin IH), 7.42 (d, 7 = 9.0 Hz, 2H), 6.91 (d, 7 = 9.0 Hz, (M+H)+
-4-yl] oxy } phenyl) - 2H), 4.88 (d, 7 = 8.2 Hz, 4H), 4.76 - 4.62 (m, IH),
l,3-dihydro-2H- 4.52 (s, IH), 3.75 (dd, 7 = 12.0, 6.6 Hz, 5H), 3.48 - pyrrolo[3,4- 3.14 (m, 2H), 1.91 (dddd, 7 = 19.4, 15.1, 7.6, 5.2 Hz, c]pyridine-2- 6H), 1.51 (dd, 7 = 20.6, 12.0 Hz, 2H)
carboxamide
947 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+))
(cyclopropylcarbony (d, 7 = 5.0 Hz, IH), 8.27 (s, IH), 7.43 (d, 7 = 8.9 Hz, m/e 407 l)piperidin-4- 3H), 6.91 (d, 7 = 9.0 Hz, 2H), 4.78 (d, 7 = 4.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4H), 4.53 (dt, 7 = 7.9, 4.0 Hz, IH), 4.06 - 3.66 (m,
dihydro-2H- 2H), 3.64 - 3.39 (m, IH), 2.08 - 1.73 (m, 3H), 1.73 - pyrrolo[3,4- 1.37 (m, 2H), 0.84 - 0.52 (m, 4H)
c]pyridine-2- carboxamide
948 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+))
(cyclopropylacetyl)p (d, 7 = 5.0 Hz, IH), 8.27 (s, IH), 7.42 (dd, 7 = 7.0, 1.8 m/e 421 iperidin-4- Hz, 2H), 6.90 (d, J = 9.0 Hz, IH), 4.81 - 4.74 (m, (M+H)+ y 1] o xy } phenyl) - 1 , 3 - 4H), 4.57 - 4.45 (m, IH), 3.93 - 3.81 (m, IH), 3.73 - dihydro-2H- 3.62 (m, IH), 2.27 (d, 7 = 6.7 Hz, 2H), 1.99 - 1.82 (m, pyrrolo[3,4- 2H), 1.68 - 1.35 (m, 2H), 1.04 - 0.87 (m, IH), 0.50 - c]pyridine-2- 0.40 (m, 2H), 0.16 - 0.07 (m, 2H)
carboxamide
949 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.83 (s, IH), 8.71 (ESI(+))
(cyclobutylcarbonyl) (d, 7 = 5.6 Hz, IH), 8.37 (s, IH), 7.82 (d, 7 = 5.6 Hz, m/e 421 piperidin-4- IH), 7.41 (d, 7 = 9.0 Hz, 2H), 6.90 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.89 (d, 7 = 9.7 Hz, 4H), 4.61 - 4.38 (m, IH),
dihydro-2H- 3.90 - 3.75 (m, IH), 3.64 - 3.46 (m, IH), 3.27 - 3.06 pyrrolo[3,4- (m, 2H), 2.12 (ddd, 7 = 13.8, 12.3, 7.5 Hz, 4H), 2.00 - c]pyridine-2- 1.77 (m, 3H), 1.74 (dd, 7 = 9.1, 4.8 Hz, IH), 1.59 - carboxamide 1.28 (m, 2H)
950 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.78 (s, IH), 8.66 (ESI(+))
(cyclopentylcarbonyl (d, 7 = 5.5 Hz, IH), 8.35 (s, IH), 7.74 (d, J = 5.4 Hz, m/e 435
)piperidin-4- IH), 7.42 (d, J = 9.0 Hz, 2H), 6.91 (d, J = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.87 (d, 7 = 4.5 Hz, 4H), 4.51 (dd, 7 = 7.7, 3.9
dihydro-2H- Hz, IH), 3.92 - 3.70 (m, 2H), 3.45 - 3.30 (m, IH),
pyrrolo[3,4- 3.21 (dd, 7 = 18.3, 8.9 Hz, IH), 2.98 (dd, 7 = 15.4, 7.5 c]pyridine-2- Hz, IH), 2.01 - 1.38 (m, 12H)
carboxamide
951 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.78 (s, IH), 8.67 (ESI(+))
(cyclopentylacetyl)pi (d, 7 = 5.4 Hz, IH), 8.35 (s, IH), 7.75 (d, 7 = 5.5 Hz, m/e 449 peridin-4- IH), 7.42 (d, 7 = 9.0 Hz, 2H), 6.91 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.87 (d, 7 = 5.1 Hz, 5H), 4.55 - 4.45 (m, IH),
dihydro-2H- 3.86 (d, 7 = 12.3 Hz, IH), 3.71 (d, 7 = 14.1 Hz, IH), pyrrolo[3,4- 3.39 - 3.08 (m, 2H), 2.34 (d, 7 = 7.1 Hz, 2H), 2.13 (dt, c]pyridine-2- 7 = 15.3, 7.6 Hz, IH), 1.90 (s, 2H), 1.74 (dt, 7 = 11.2, carboxamide 6.5 Hz, 2H), 1.65 - 1.36 (m, 6H), 1.23 - 1.02 (m, 2H)
952 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.78 (s, IH), 8.66 (ESI(+))
(cyclohexylcarbonyl (d, 7 = 5.4 Hz, IH), 8.35 (s, IH), 7.74 (d, 7 = 5.3 Hz, m/e 449
)piperidin-4- IH), 7.42 (d, 7 = 9.0 Hz, 2H), 6.91 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.87 (d, 7 = 4.5 Hz, 4H), 4.54 - 4.44 (m, IH),
dihydro-2H- 3.83 (s, 2H), 3.17 (d, 7 = 0.9 Hz, 2H), 2.63 - 2.52 (m, pyrrolo[3,4- IH), 1.91 (s, 3H), 1.61 (dd, 7 = 38.7, 30.1 Hz, 7H),
c]pyridine-2- 1.43 - 1.02 (m, 7H)
carboxamide
987 N-(4-{ [l-(3,3,3- ¾ NMR (300 MHz, DMSO-d6) δ 8.77 (s, IH), 8.65 (ESI(+)) trifluoropropanoyl)a (d, 7 = 5.4 Hz, IH), 8.38 (s, IH), 7.72 (d, 7 = 5.5 Hz, m/e 421 zetidin-3- 2H), 7.45 (d, 7 = 9.1 Hz, 2H), 6.78 (d, 7 = 9.1 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 5.06 - 4.93 (m, IH), 4.87 (d, 7 = 3.6 Hz, 4H),
dihydro-2H- 4.60 (dd, 7 = 8.6, 6.5 Hz, IH), 4.34 (dd, 7 = 11.0, 6.1 pyrrolo[3,4- Hz, IH), 4.15 (dd, 7 = 9.6, 2.9 Hz, IH), 3.81 (dd, 7 =
c]pyridine-2- 10.7, 3.8 Hz, IH), 3.40 (q, 7 = 11.2 Hz, 2H)
carboxamide
988 N-(4-{ [l-(4,4,4- ¾ NMR (300 MHz, DMSO-d6) δ 8.69 (s, IH), 8.58 (ESI(+)) trifluorobutanoyl)aze (d, 7 = 5.3 Hz, IH), 8.34 (s, IH), 7.58 (d, 7 = 5.2 Hz, m/e 435 tidin-3- IH), 7.45 (d, 7 = 9.1 Hz, 2H), 6.78 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.98 (dd, 7 = 8.4, 4.4 Hz, IH), 4.82 (s, 4H), 4.66 dihydro-2H- - 4.49 (m, IH), 4.31 (dd, 7 = 10.6, 6.5 Hz, IH), 4.13 pyrrolo[3,4- (dd, 7 = 9.4, 3.5 Hz, IH), 3.78 (dd, 7 = 10.5, 3.7 Hz, c]pyridine-2- 2H), 2.40 - 2.29 (m, 4H)
carboxamide 989 Ν-(4-{ [1- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.57 (s, (ESI(+)) (tetrahydrofuran-2- IH), 8.47 (d, 7 = 5.0 Hz, IH), 8.06 (s, IH), 7.50 - 7.39 m/e 409 ylcarbonyl) azetidin- (m, 2H), 7.37 (d, J = 4.9 Hz, IH), 6.82 - 6.70 (m, 2H), (M+H)+ 3-yl] oxy jphenyl)- 4.98 (tt, 7 = 6.5, 4.1 Hz, IH), 4.83 - 4.73 (m, 5H),
l,3-dihydro-2H- 4.34 (dd, 7 = 7.6, 6.2 Hz, 2H), 3.85 - 3.61 (m, 4H),
pyrrolo[3,4- 2.10 - 1.90 (m, 2H), 1.90 - 1.70 (m, 2H)
c]pyridine-2- carboxamide
990 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.57 (s, (ESI(+)) (tetrahydrofuran-3- IH), 8.47 (d, 7 = 5.0 Hz, IH), 8.06 (s, IH), 7.50 - 7.41 m/e 423 ylacetyl) azetidin-3 - (m, 2H), 7.37 (d, 7 = 5.0 Hz, IH), 6.92 - 6.66 (m, 2H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 5.03 - 4.91 (m, IH), 4.83 - 4.73 (m, 5H), 3.78 (dd, 7 =
dihydro-2H- 8.3, 7.1 Hz, IH), 3.71 (td, 7 = 8.1, 5.4 Hz, IH), 3.62
pyrrolo[3,4- (dd, 7 = 15.4, 7.4 Hz, IH), 3.27 (dd, 7 = 8.4, 6.5 Hz, c]pyridine-2- IH), 2.24 - 2.09 (m, 3H), 2.05 - 1.89 (m, IH), 1.50
carboxamide (dt, 7 = 14.7, 7.0 Hz, IH)
991 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.64 (ESI(+))
(cyclobutylcarbonyl) (d, 7 = 5.4 Hz, IH), 8.38 (s, IH), 7.70 (d, 7 = 5.4 Hz, m/e 393 azetidin-3- IH), 7.44 (d, 7 = 9.0 Hz, 2H), 6.77 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 5.05 - 4.90 (m, IH), 4.86 (s, 4H), 4.52 - 4.40 (m, dihydro-2H- IH), 4.30 - 4.20 (m, IH), 3.97 (dd, 7 = 9.5, 3.8 Hz,
pyrrolo[3,4- IH), 3.74 (dd, 7 = 10.4, 3.8 Hz, IH), 3.12 (p, 7 = 8.4 c]pyridine-2- Hz, IH), 2.19 - 1.96 (m, 4H), 1.96 - 1.79 (m, IH),
carboxamide 1.79 - 1.62 (m, IH)
992 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.77 (s, IH), 8.66 (ESI(+))
(cyclopentylcarbonyl (d, 7 = 5.4 Hz, IH), 8.38 (s, IH), 7.73 (d, 7 = 5.3 Hz, m/e 407
)azetidin-3- IH), 7.45 (d, 7 = 9.0 Hz, 2H), 6.78 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.97 (t, 7 = 5.1 Hz, IH), 4.87 (d, 7 = 3.9 Hz, 4H), dihydro-2H- 4.64 - 4.47 (m, IH), 4.27 (dd, 7 = 10.3, 6.6 Hz, IH), pyrrolo[3,4- 4.14 - 4.02 (m, IH), 3.82 - 3.65 (m, IH), 2.76 - 2.55 c]pyridine-2- (m, IH), 1.89 - 1.39 (m, 8H)
carboxamide
993 N-(4-{ [l-(3- ¾ NMR (300 MHz, DMSO-d6) δ 8.80 (s, IH), 8.68 (ESI(+)) phenylpropanoyl)pyr (d, 7 = 5.4 Hz, IH), 8.37 (s, IH), 7.77 (d, 7 = 5.3 Hz, m/e 457 rolidin-3- IH), 7.49 - 7.37 (m, 2H), 7.33 - 7.11 (m, 5H), 6.87 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (dd, 7 = 9.1, 2.3 Hz, 2H), 4.91 (dd, 7 = 22.6, 11.0 Hz, dihydro-2H- 5H), 3.51 (d, 7 = 9.0 Hz, 4H), 2.81 (dd, 7 = 13.6, 7.3 pyrrolo[3,4- Hz, 2H), 2.63 - 2.51 (m, 2H), 2.07 (dd, 7 = 17.7, 8.2 c]pyridine-2- Hz, 2H)
carboxamide
994 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.49 (ESI(+))
(phenylacetyl)pyrroli (d, 7 = 5.0 Hz, IH), 8.29 (s, IH), 7.43 (dd, 7 = 6.8, 4.6 m/e 443 din-3- Hz, 3H), 7.38 - 7.10 (m, 5H), 6.86 (dd, 7 = 8.9, 1.9 (M+H)+ yl] o xy } phenyl) - 1 , 3 - Hz, 2H), 4.98 (d, 7 = 21.6 Hz, IH), 4.78 (d, 7 = 4.4
dihydro-2H- Hz, 4H), 3.59 (dd, 7 = 29.8, 8.4 Hz, 6H), 2.24 - 1.94 pyrrolo[3,4- (m, 2H)
c]pyridine-2- carboxamide
995 N-[4-({ l-[(4- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.49 (ESI(+)) methoxyphenyl) acet (d, 7 = 5.0 Hz, IH), 8.29 (s, IH), 7.52 - 7.34 (m, 3H), m/e 473 yl]pyrrolidin-3- 7.14 (t, 7 = 8.1 Hz, 2H), 6.95 - 6.73 (m, 4H), 4.97 (d, (M+H)+ yl } oxy)phenyl] -1,3- 7 = 21.7 Hz, IH), 4.78 (d, 7 = 4.4 Hz, 4H), 3.70 (t, 7 =
dihydro-2H- 10.2 Hz, 5H), 3.63 - 3.47 (m, 4H), 2.31 - 1.91 (m,
pyrrolo[3,4- 2H) c]pyridine-2- carboxamide
996 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.82 (s, IH), 8.70 (ESI(+))
(methoxyacetyl)pyrr (d, J = 5.5 Hz, IH), 8.39 (s, IH), 7.81 (d, 7 = 5.3 Hz, m/e 397 olidin-3- IH), 7.44 (d, 7 = 9.0 Hz, 2H), 6.96 - 6.81 (m, 2H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4.91 (t, 7 = 9.8 Hz, 5H), 4.05 (s, IH), 3.99 (s, IH),
dihydro-2H- 3.76 - 3.32 (m, 4H), 3.30 (s, 1.5H), 3.28 (s, 1.5H),
pyrrolo[3,4- 2.13 (dd, J = 7.4, 3.7 Hz, IH), 2.07 - 1.96 (m, IH)
c]pyridine-2- carboxamide
997 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+))
(cyclopropylcarbony (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.53 - 7.32 (m, 3H), m/e 393 l)pyrrolidin-3- 6.89 (dd, 7 = 9.0, 7.4 Hz, 2H), 5.03 (dd, 7 = 18.0, 16.5 (M+H)+ yl] o xy } phenyl) - 1 , 3 - Hz, IH), 4.78 (d, 7 = 3.8 Hz, 4H), 3.98 - 3.61 (m,
dihydro-2H- 2H), 3.51 (m, 2H), 2.31 - 1.91 (m, 2H), 1.76 (d, 7 =
pyrrolo[3,4- 20.7 Hz, IH), 0.83 - 0.59 (m, 4H)
c]pyridine-2- carboxamide
998 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.80 (s, IH), 8.68 (ESI(+))
(cyclohexylcarbonyl (d, 7 = 5.5 Hz, IH), 8.37 (s, IH), 7.77 (d, 7 = 5.0 Hz, m/e 435
)pyrrolidin-3- IH), 7.43 (dd, 7 = 9.0, 1.8 Hz, 2H), 6.88 (dd, 7 = 9.0, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 7.5 Hz, 2H), 5.01 (s, IH), 4.89 (t, 7 = 8.6 Hz, 4H),
dihydro-2H- 3.82 - 3.25 (m, 4H), 2.43 - 1.93 (m, 3H), 1.67 (d, 7 =
pyrrolo[3,4- 10.0 Hz, 5H), 1.47 - 1.03 (m, 5H)
c]pyridine-2- carboxamide
999 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.65 (ESI(+))
(cyclopentylacetyl)p (d, 7 = 5.4 Hz, IH), 8.35 (s, IH), 7.71 (d, 7 = 5.2 Hz, m/e 435 yrrolidin-3- IH), 7.44 (d, 7 = 8.6 Hz, 2H), 7.02 - 6.78 (m, 2H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4.96 (d, 7 = 21.3 Hz, IH), 4.86 (d, 7 = 2.2 Hz, 4H),
dihydro-2H- 3.67 - 3.44 (m, 4H), 2.31 - 2.01 (m, 5H), 1.75 (s, 2H), pyrrolo[3,4- 1.62 - 1.38 (m, 4H), 1.10 (dd, 7 = 13.0, 5.9 Hz, 2H)
c]pyridine-2- carboxamide
1000 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.64 (ESI(+))
(cyclopentylcarbonyl (d, 7 = 5.4 Hz, IH), 8.35 (s, IH), 7.70 (d, 7 = 5.0 Hz, m/e 421
)pyrrolidin-3- IH), 7.54 - 7.34 (m, 2H), 6.97 - 6.77 (m, 2H), 4.97 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (m, IH), 4.86 (s, 4H), 3.69 - 3.36 (m, 4H), 2.95 - 2.68 dihydro-2H- (m, IH), 2.11 (ddd, 7 = 17.8, 8.5, 4.2 Hz, 2H), 1.86 - pyrrolo[3,4- 1.41 (m, 8H)
c]pyridine-2- carboxamide
1001 N-{4-[(l- ¾ NMR (300 MHz, DMSO-d6) δ 8.78 (d, 7 = 2.9 Hz, (ESI(+)) benzoylpyrrolidin-3 - IH), 8.67 (d, 7 = 4.0 Hz, IH), 8.36 (d, 7 = 14.5 Hz, m/e 429 yl)o xy] phenyl } - 1 , 3 - IH), 7.75 (d, 7 = 4.4 Hz, IH), 7.61 - 7.33 (m, 7H), (M+H)+ dihydro-2H- 6.88 (dd, 7 = 27.8, 8.9 Hz, 2H), 4.98 (m, IH), 4.87 (m, pyrrolo[3,4- 4H), 3.90 - 3.75 (m, IH), 3.71 - 3.57 (m, 2H), 3.46
c]pyridine-2- (d, 7 = 24.5 Hz, IH), 2.11 (d, 7 = 13.7 Hz, 2H)
carboxamide
1002 N-(4-{ [l-(3- ¾ NMR (300 MHz, DMSO-d6) δ 8.73 (s, IH), 8.61 (ESI(+)) ethoxypropanoyl)pyr (d, 7 = 5.3 Hz, IH), 8.34 (s, IH), 7.65 (d, 7 = 5.1 Hz, m/e 425 rolidin-3- IH), 7.44 (dd, 7 = 9.0, 1.1 Hz, 2H), 6.88 (dd, 7 = 9.0, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 5.3 Hz, 2H), 4.97 (d, 7 = 19.1 Hz, IH), 4.84 (s, 4H), dihydro-2H- 3.62 - 3.47 (m, 6H), 3.47 - 3.32 (m, 4H), 2.19 - 2.09 pyrrolo[3,4- (m, IH), 2.09 - 2.00 (m, IH), 1.07 (dt, J = 9.8, 7.0 Hz, c]pyridine-2- 3H)
carboxamide
1003 N-[4-({ l-[(2- ¾ NMR (300 MHz, DMSO-d6) δ 8.78 (s, IH), 8.66 (ESI(+)) methylcyclopropyl)c (d, 7 = 5.4 Hz, IH), 8.36 (s, IH), 7.74 (d, 7 = 5.3 Hz, m/e 407 arbonyl]pyrrolidin- IH), 7.54 - 7.35 (m, 2H), 6.88 (td, 7 = 9.9, 5.3 Hz, (M+H)+
3 -yl } oxy)phenyl] - 2H), 4.99 (d, 7 = 30.6 Hz, IH), 4.87 (d, 7 = 4.1 Hz,
l,3-dihydro-2H- 4H), 3.94 - 3.58 (m, 2H), 3.52 (t, 7 = 5.2 Hz, 2H),
pyrrolo[3,4- 2.29 - 2.01 (m, 2H), 1.57 - 1.42 (m, IH), 1.12 - 1.01 c]pyridine-2- (m, 4H), 0.94 (ddd, 7 = 9.5, 7.6, 4.7 Hz, IH), 0.62 - carboxamide 0.50 (m, IH)
1004 N-[4-({ l-[(l- ¾ NMR (300 MHz, DMSO-d6) δ 8.77 (s, IH), 8.65 (ESI(+)) methylcyclopropyl)c (d, 7 = 5.4 Hz, IH), 8.36 (s, IH), 7.72 (d, J = 5.4 Hz, m/e 407 arbonyl]pyrrolidin- IH), 7.57 - 7.37 (m, 2H), 6.88 (d, J = 9.0 Hz, 2H), (M+H)+
3 -yl } oxy)phenyl] - 4.97 (s, IH), 4.87 (d, J = 3.5 Hz, 4H), 4.26 (s, 2H),
l,3-dihydro-2H- 3.77 (s, 2H), 2.10 (s, 2H), 1.26 - 1.17 (m, 3H), 0.92 - pyrrolo[3,4- 0.80 (m, IH), 0.66 (s, IH), 0.48 (s, 2H)
c]pyridine-2- carboxamide
1005 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.75 (s, IH), 8.63 (ESI(+))
(cyclobutylcarbonyl) (d, J = 53 Hz, IH), 8.34 (s, IH), 7.68 (d, 7 = 5.1 Hz, m/e 407 pyrrolidin-3- IH), 7.49 - 7.34 (m, 2H), 6.94 - 6.76 (m, 2H), 4.95 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (d, 7 = 17.9 Hz, IH), 4.85 (s, 4H), 3.67 - 3.10 (m,
dihydro-2H- 5H), 2.10 (dtd, 7 = 19.7, 15.3, 8.2 Hz, 6H), 1.96 - 1.64 pyrrolo[3,4- (m, 2H)
c]pyridine-2- carboxamide
1006 N-(4-{ [l-(3- ¾ NMR (300 MHz, DMSO-d6) δ 8.79 (s, IH), 8.67 (ESI(+)) methylbutanoyl)pyrr (d, 7 = 5.4 Hz, IH), 8.37 (s, IH), 7.75 (d, 7 = 5.4 Hz, m/e 409 olidin-3- IH), 7.44 (d, 7 = 9.0 Hz, 2H), 6.96 - 6.76 (m, 2H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4.97 (d, 7 = 21.3 Hz, IH), 4.87 (d, 7 = 5.4 Hz, 4H),
dihydro-2H- 3.83 - 3.24 (m, 4H), 2.25 - 1.98 (m, 5H), 0.98 - 0.81 pyrrolo[3,4- (m, 6H)
c]pyridine-2- carboxamide
1007 N-(4-{ [l-(2- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.65 (ESI(+)) methylpropanoyl)pyr (d, 7 = 5.4 Hz, IH), 8.36 (s, IH), 7.71 (d, 7 = 5.0 Hz, m/e 395 rolidin-3- IH), 7.44 (d, 7 = 8.8 Hz, 2H), 6.88 (dd, 7 = 9.0, 6.9 (M+H)+ yl] o xy } phenyl) - 1 , 3 - Hz, 2H), 4.97 (d, 7 = 25.9 Hz, IH), 4.86 (d, 7 = 2.6
dihydro-2H- Hz, 4H), 3.80 - 3.26 (m, 4H), 2.64 (ddt, 7 = 27.4,
pyrrolo[3,4- 13.9, 7.1 Hz, IH), 2.31 - 2.00 (m, 2H), 0.99 (ddd, 7 =
c]pyridine-2- 16.0, 9.0, 4.2 Hz, 6H)
carboxamide
1008 N- {4-[(l- ¾ NMR (300 MHz, DMSO-d6) δ 8.79 (s, IH), 8.67 (ESI(+)) acetylpyrrolidin-3- (d, 7 = 5.5 Hz, IH), 8.37 (s, IH), 7.75 (d, 7 = 5.4 Hz, m/e 367 yl)o xy] phenyl } - 1 , 3 - IH), 7.44 (d, 7 = 8.9 Hz, 2H), 6.95 - 6.79 (m, 2H), (M+H)+ dihydro-2H- 5.07 - 4.90 (m, IH), 4.87 (d, 7 = 5.3 Hz, 4H), 3.83 - pyrrolo[3,4- 3.22 (m, 4H), 2.26 - 2.00 (m, 2H), 1.97 (s, 1.5H), 1.93 c]pyridine-2- (s, 1.5H)
carboxamide
1009 N-(4-{ [l-(4,4,4- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.64 (ESI(+)) trifluorobutanoyl)pyr (d, 7 = 5.4 Hz, IH), 8.36 (s, IH), 7.71 (d, 7 = 5.4 Hz, m/e 449 rolidin-3- IH), 7.44 (dd, 7 = 9.0, 1.7 Hz, 2H), 6.88 (dd, 7 = 8.9, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 6.4 Hz, 2H), 4.99 (d, 7 = 21.2 Hz, IH), 4.86 (d, 7 = 2.1 dihydro-2H- Hz, 4H), 3.85 - 3.29 (m, 4H), 2.56 (d, 7 = 5.1 Hz,
pyrrolo[3,4- 4H), 2.11 (dd, 7 = 24.1, 8.1 Hz, 2H)
c]pyridine-2- carboxamide
1010 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.77 (s, IH), 8.66 (ESI(+))
(tetrahydrofuran-3- (d, 7 = 5.4 Hz, IH), 8.37 (s, IH), 7.73 (d, 7 = 5.1 Hz, m/e 423 ylcarbonyl)pyrrolidi IH), 7.44 (dd, 7 = 8.9, 1.6 Hz, 2H), 6.89 (dd, 7 = 8.8, (M+H)+ n-3 -yl] oxy } phenyl) - 6.9 Hz, 2H), 4.98 (d, 7 = 21.7 Hz, IH), 4.86 (d, 7 = 3.8 l,3-dihydro-2H- Hz, 4H), 3.95 - 3.46 (m, 8H), 3.20 (dd, 7 = 14.8, 7.8 pyrrolo[3,4- Hz, IH), 1.97 (d, 7 = 7.5 Hz, 4H)
c]pyridine-2- carboxamide
1011 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.80 (s, IH), 8.68 (ESI(+))
(tetrahydrofuran-2- (d, 7 = 5.5 Hz, IH), 8.38 (s, IH), 7.78 (d, 7 = 5.4 Hz, m/e 423 ylcarbonyl)pyrrolidi IH), 7.44 (d, 7 = 9.0 Hz, 2H), 6.88 (dd, 7 = 8.2, 4.6 (M+H)+ n-3 -yl] oxy } phenyl) - Hz, 2H), 4.98 (d, 7 = 23.0 Hz, IH), 4.88 (d, 7 = 7.4
l,3-dihydro-2H- Hz, 4H), 4.51 (dt, 7 = 13.2, 6.2 Hz, 2H), 3.89 - 3.46
pyrrolo[3,4- (m, 5H), 2.33 - 1.67 (m, 6H)
c]pyridine-2- carboxamide
1012 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.79 (s, IH), 8.67 (ESI(+))
(ethoxyacetyl)pyrroli (d, 7 = 5.5 Hz, IH), 8.38 (s, IH), 7.76 (d, 7 = 5.1 Hz, m/e 411 din-3- IH), 7.44 (d, 7 = 9.0 Hz, 2H), 6.94 - 6.76 (m, 2H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4.98 (d, 7 = 22.7 Hz, 2H), 4.87 (d, 7 = 5.8 Hz, 5H),
dihydro-2H- 4.07 (s, IH), 4.01 (s, IH), 3.75 - 3.27 (m, 7H), 2.24 - pyrrolo[3,4- 1.98 (m, 2H), 1.11 (dt, 7 = 10.8, 6.9 Hz, 3H)
c]pyridine-2- carboxamide
1026 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.77 (s, IH), 8.65 (ESI(+))
(cyclohexylacetyl)pi (d, 7 = 5.4 Hz, IH), 8.34 (s, IH), 7.72 (d, 7 = 5.4 Hz, m/e 463 peridin-4- IH), 7.50 - 7.34 (m, 2H), 6.99 - 6.82 (m, 2H), 4.86 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (d, 7 = 3.5 Hz, 4H), 4.56 - 4.45 (m, IH), 3.60-3.89 (m, dihydro-2H- 2H), 3.39 - 3.14 (m, 2H), 2.20 (d, 7 = 6.7 Hz, 2H),
pyrrolo[3,4- 1.90 (s, 2H), 1.72 - 1.39 (m, 8H), 1.29 - 1.06 (m, 3H), c]pyridine-2- 0.94 (t, 7 = 11.6 Hz, 2H)
carboxamide
1027 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.79 (s, IH), 8.67 (ESI(+))
(tetrahydro-2H- (d, 7 = 5.5 Hz, IH), 8.36 (s, IH), 7.76 (d, 7 = 5.5 Hz, m/e 465 pyran-4- IH), 7.42 (d, 7 = 9.0 Hz, 2H), 6.91 (d, 7 = 9.0 Hz, (M+H)+ ylacetyl)piperidin-4- 2H), 4.87 (d, 7 = 6.1 Hz, 5H), 4.50 (dd, 7 = 7.7, 3.9
yl] o xy } phenyl) - 1 , 3 - Hz, 2H), 3.81 (ddd, 7 = 27.5, 21.4, 10.7 Hz, 4H), 3.39 dihydro-2H- - 3.14 (m, 4H), 2.27 (d, 7 = 6.5 Hz, 2H), 2.01 - 1.77 pyrrolo[3,4- (m, 3H), 1.65 - 1.35 (m, 4H), 1.19 (tdd, 7 = 13.5, 9.2, c]pyridine-2- 4.4 Hz, 2H)
carboxamide
1037 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.75 (s, IH), 8.63 (ESI(+)) (tetrahydrofuran-2- (d, 7 = 5.4 Hz, IH), 8.37 (s, IH), 7.68 (d, 7 = 5.2 Hz, m/e 423 ylacetyl) azetidin-3 - IH), 7.45 (d, 7 = 9.0 Hz, 2H), 6.78 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.97 (dd, 7 = 10.3, 6.6 Hz, IH), 4.85 (s, 4H), 4.63 dihydro-2H- - 4.48 (m, IH), 4.27 (s, 2H), 4.05 (dd, 7 = 13.5, 6.8
pyrrolo[3,4- Hz, 2H), 3.62 - 3.45 (m, 2H), 2.28 (dddd, 7 = 20.3,
c]pyridine-2- 14.5, 10.4, 7.5 Hz, 3H), 2.06 - 1.90 (m, IH), 1.81 (dd, carboxamide 7 = 13.8, 6.4 Hz, 2H), 1.47 (ddd, 7 = 15.7, 11.8, 7.2
Hz, IH) 1038 Ν-(4-{ [1- ¾ NMR (300 MHz, DMSO-d6) δ 8.77 (s, IH), 8.65 (ESI(+))
(tetrahydro-2H- (d, J = 5.4 Hz, IH), 8.38 (s, IH), 7.71 (d, 7 = 5.5 Hz, m/e 437 pyran-4- IH), 7.45 (d, 7 = 9.1 Hz, 2H), 6.78 (d, 7 = 9.0 Hz, (M+H)+ ylacetyl) azetidin-3 - 2H), 4.96 (s, IH), 4.86 (d, 7 = 3.0 Hz, 4H), 4.62 - 4.47 yl] o xy } phenyl) - 1 , 3 - (m, IH), 4.27 (dd, 7 = 10.7, 6.3 Hz, IH), 4.03 (dd, 7 =
dihydro-2H- 14.3, 7.2 Hz, IH), 3.76 (dd, 7 = 18.7, 8.0 Hz, 3H),
pyrrolo[3,4- 3.25 (dd, 7 = 27.4, 15.8 Hz, 2H), 2.01 (t, 7 = 7.5 Hz, c]pyridine-2- 2H), 1.89 (s, IH), 1.56 (d, 7 = 11.3 Hz, 2H), 1.34 - carboxamide 1.03 (m, 2H)
1039 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.70 (s, IH), 8.59 (ESI(+)) (morpholin-4- (d, J = 53 Hz, IH), 8.37 (s, IH), 7.59 (d, 7 = 5.1 Hz, m/e 438 ylacetyl) azetidin-3 - IH), 7.47 (d, J = 9.0 Hz, 2H), 6.80 (d, J = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 5.06 (s, IH), 4.83 (s, 4H), 4.65 - 4.53 (m, IH), dihydro-2H- 4.44 (dd, J = 10.8, 6.2 Hz, IH), 4.21 - 4.12 (m, 2H), pyrrolo[3,4- 4.07 (s, 5H), 3.23 (s, 4H)
c]pyridine-2- carboxamide
1040 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.77 (s, IH), 8.66 (ESI(+))
(cyclohexylacetyl) az (d, J = 5.4 Hz, IH), 8.38 (s, IH), 7.73 (d, J = 5.4 Hz, m/e 435 etidin-3- IH), 7.45 (d, J = 9.0 Hz, 2H), 6.78 (d, J = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 5.05 - 4.91 (m, IH), 4.87 (d, J = 3.9 Hz, 4H),
dihydro-2H- 4.62 - 4.45 (m, IH), 4.27 (dd, J = 10.4, 6.5 Hz, IH), pyrrolo[3,4- 4.04 (dd, 7 = 9.1, 3.5 Hz, IH), 3.74 (dd, 7 = 10.6, 3.7 c]pyridine-2- Hz, IH), 2.05 - 1.88 (m, 2H), 1.64 (d, 7 = 12.0 Hz,
carboxamide 6H), 1.16 (m, 3H), 0.94 (t, 7 = 11.8 Hz, 2H)
1041 N-(4-{ [l-(2- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.65 (ESI(+)) methylbutanoyl)azeti (d, 7 = 5.4 Hz, IH), 8.38 (s, IH), 7.71 (d, 7 = 5.4 Hz, m/e 395 din-3- IH), 7.51 - 7.37 (m, 2H), 6.79 (d, 7 = 9.0 Hz, 2H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4.98 (d, 7 = 2.5 Hz, IH), 4.86 (d, 7 = 2.9 Hz, 4H), 4.64 dihydro-2H- - 4.48 (m, IH), 4.33 - 4.21 (m, IH), 4.12 - 4.02 (m, pyrrolo[3,4- IH), 3.76 (dd, 7 = 10.5, 3.8 Hz, IH), 2.29 (dd, 7 =
c]pyridine-2- 13.8, 6.9 Hz, IH), 1.58 - 1.39 (m, IH), 1.39 - 1.20
carboxamide (m, IH), 0.97 (dd, 7 = 6.8, 4.1 Hz, 3H), 0.82 (q, 7 =
7.3 Hz, 3H)
1042 N-(4-{ [l-(2,2- ¾ NMR (300 MHz, DMSO-d6) δ 8.78 (s, IH), 8.67 (ESI(+)) dime thy lprop ano yl) a (d, 7 = 5.5 Hz, IH), 8.39 (s, IH), 7.74 (d, 7 = 5.4 Hz, m/e 395 zetidin-3- IH), 7.54 - 7.33 (m, 2H), 6.82 - 6.64 (m, 2H), 4.94 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (td, 7 = 6.3, 3.2 Hz, IH), 4.87 (d, 7 = 4.8 Hz, 4H), 4.55 dihydro-2H- - 4.12 (m, 4H), 1.12 (s, 9H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1043 N-(4-{ [l-(3,3- ¾ NMR (300 MHz, DMSO-d6) δ 8.80 (s, IH), 8.68 (ESI(+)) dimethylbutanoyl)az (d, 7 = 5.5 Hz, IH), 8.39 (s, IH), 7.77 (d, 7 = 5.5 Hz, m/e 409 etidin-3- IH), 7.44 (d, 7 = 9.0 Hz, 2H), 6.78 (d, 7 = 9.0 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 5.01 - 4.90 (m, IH), 4.88 (d, 7 = 6.5 Hz, 4H),
dihydro-2H- 4.60 - 4.45 (m, IH), 4.27 (dd, 7 = 10.4, 6.5 Hz, IH), pyrrolo[3,4- 4.04 (dd, 7 = 8.9, 5.2 Hz, IH), 3.74 (dd, 7 = 10.6, 3.8 c]pyridine-2- Hz, IH), 1.96 (s, 2H), 0.98 (s, 9H)
carboxamide
1044 N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.64 (ESI(+))
(tricyclo[3.3.1.1 -3,7 (d, 7 = 5.4 Hz, IH), 8.38 (s, IH), 7.70 (d, 7 = 5.4 Hz, m/e 487 ~]dec-l- IH), 7.52 - 7.36 (m, 2H), 6.82 - 6.69 (m, 2H), 4.97 - (M+H)+ ylacetyl) azetidin-3 - 4.90 (m, IH), 4.86 (s, 4H), 4.61 - 4.47 (m, IH), 4.26 y 1] o xy } phenyl) - 1 , 3 - (dd, 7 = 10.3, 6.4 Hz, IH), 4.08 - 3.99 (m, IH), 3.74 dihydro-2H- (dd, 7 = 10.6, 3.9 Hz, IH), 1.92 (s, 2H), 1.83 (s, 2H), pyrrolo[3,4- 1.70 - 1.52 (m, 13H)
c]pyridine-2- carboxamide
1045 N-[4-({ l-[(4- ¾ NMR (300 MHz, DMSO-d6) δ 8.76 (s, IH), 8.65 (ESI(+)) methoxycyclohexyl) (d, 7 = 5.4 Hz, IH), 8.38 (s, IH), 7.71 (d, 7 = 5.4 Hz, m/e 451 carbonyl] azetidin-3- IH), 7.45 (d, 7 = 9.0 Hz, 2H), 6.78 (d, 7 = 9.0 Hz, (M+H)+ yl } oxy)phenyl] -1,3- 2H), 4.96 (s, IH), 4.86 (d, 7 = 2.7 Hz, 4H), 4.58 (s,
dihydro-2H- IH), 4.31 - 4.19 (m, IH), 4.05 (dd, 7 = 14.5, 7.4 Hz, pyrrolo[3,4- IH), 3.74 (d, 7 = 10.3 Hz, IH), 3.36 (s, IH), 3.19 (s, c]pyridine-2- 3H), 2.27 (s, IH), 1.81 (s, 2H), 1.57 (t, 7 = 12.2 Hz,
carboxamide 2H), 1.38 (s, 4H)
1288 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.57 (s, (ESI(+))
(tetrahydro-2H- IH), 8.47 (d, 7 = 5.0 Hz, IH), 8.06 (s, IH), 7.50 - 7.40 m/e 423 pyran-2- (m, 2H), 7.37 (d, 7 = 5.0 Hz, IH), 6.82 - 6.70 (m, 2H), (M+H)+ ylcarbonyl) azetidin- 4.97 (tt, 7 = 6.4, 4.0 Hz, IH), 4.83 - 4.73 (m, 4H),
3-yl] oxy jphenyl)- 4.69 - 4.44 (m, IH), 4.44 - 4.19 (m, IH), 4.21 - 3.98 l,3-dihydro-2H- (m, IH), 3.89 (ddd, 7 = 14.6, 10.3, 2.3 Hz, 3H), 3.48 - pyrrolo[3,4- 3.33 (m, IH), 1.79 (dt, 7 = 6.0, 4.3 Hz, IH), 1.70 (dt, 7
c]pyridine-2- = 6.7, 2.5 Hz, IH), 1.61 - 1.39 (m, 4H)
carboxamide
1289 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.57 (s, (ESI(+))
(tetrahydro-2H- IH), 8.47 (d, 7 = 5.0 Hz, IH), 8.08 - 7.96 (m, IH), m/e 437 pyran-2- 7.46 - 7.39 (m, 2H), 7.37 (d, 7 = 5.2 Hz, IH), 6.84 (t, (M+H)+ ylcarbonyl)pyrrolidi 7 = 5.9 Hz, 2H), 5.00 - 4.86 (m, IH), 4.86 - 4.72 (m, n-3 -yl] oxy } phenyl) - 4H), 4.08 - 3.92 (m, IH), 3.92 - 3.36 (m, 6H), 2.21 - l,3-dihydro-2H- 1.95 (m, 2H), 1.69 - 1.40 (m, 6H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1292 N-{4-[(l- ¾ NMR (300 MHz, DMSO-d6) δ 8.83 (s, IH), 8.71 (ESI(+)) acetylpiperidin-3- (d, 7 = 5.4 Hz, IH), 8.38 (s, IH), 7.83 (dd, 7 = 5.2, 3.0 m/e 381 yl)o xy] phenyl } - 1 , 3 - Hz, IH), 7.42 (dd, 7 = 8.9, 6.6 Hz, 2H), 6.89 (t, 7 = 8.5 (M+H)+ dihydro-2H- Hz, 2H), 4.89 (d, 7 = 9.6 Hz, 4H), 4.43 (s, IH), 4.22 - pyrrolo[3,4- 3.94 (m, IH), 3.67 - 3.47 (m, 2H), 3.36 - 3.02 (m,
c]pyridine-2- IH), 2.02 (s, 1.5H), 1.87 (s, 1.5H), 1.83 - 1.32 (m,
carboxamide 3H)
1293 N-{4-[(l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.66 (s, (ESI(+)) butanoylpiperidin-3- IH), 8.55 (d, 7 = 5.3 Hz, IH), 8.07 (s, IH), 7.54 (d, 7 m/e 409 yl)o xy] phenyl } - 1 , 3 - = 5.1 Hz, IH), 7.41 (d, 7 = 8.9 Hz, 2H), 6.95 - 6.70 (M+H)+ dihydro-2H- (m, 2H), 4.83 (s, 4H), 4.23 (bs, 2H), 3.45 (bs, 2H),
pyrrolo[3,4- 2.24 (bs, 2H), 1.96 (bs, IH), 1.73 (bs, 2H), 1.51 (dt, 7
c]pyridine-2- = 14.8, 7.4 Hz, 3H), 0.87 (t, 7 = 7.4 Hz, 3H)
carboxamide
1294 N-(4-{ [l-(3- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.65 (s, (ESI(+)) methylbutanoyl)pipe IH), 8.54 (d, 7 = 5.2 Hz, IH), 8.07 (s, IH), 7.52 (d, 7 m/e 423 ridin-3- = 5.2 Hz, IH), 7.41 (d, 7 = 8.9 Hz, 2H), 6.92 - 6.79 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (m, 2H), 4.82 (s, 4H), 4.25 (bs, 2H), 3.46 (bs, 2H),
dihydro-2H- 2.14 (s, 2H), 2.05 - 1.90 (m, 2H), 1.73 (bs, 2H), 1.45 pyrrolo[3,4- (bs, IH), 0.90 (dd, 7 = 9.3, 6.5 Hz, 6H)
c]pyridine-2- carboxamide
1295 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C ) δ 8.64 (ESI(+)) (methoxyacetyl)pipe (s, IH), 8.54 (d, 7 = 5.2 Hz, IH), 8.07 (s, IH), 7.51 (d, m/e 411 ridin-3- 7 = 5.1 Hz, 1H), 7.42 (d, 7 = 9.0 Hz, 2H), 6.86 (d, 7 = (M+H)+ y 1] o xy } phenyl) - 1 , 3 - 9.0 Hz, 2H), 4.82 (s, 4H), 4.26 (bs, IH), 4.05 (d, 7 =
dihydro-2H- 13.6 Hz, IH), 3.96 (s, IH), 3.42 (m, 4H), 3.27 (bs,
pyrrolo[3,4- 3H), 1.93 (d, 7 = 28.0 Hz, IH), 1.74 (bs, 2H), 1.49 (bs, c]pyridine-2- IH)
carboxamide
1296 N-(4-{ [l-(2- ¾ NMR (400 MHz, DMSO, Temp = 90 °C ) δ 8.64 (ESI(+)) methylbutanoyl)pipe (s, IH), 8.53 (d, 7 = 5.1 Hz, IH), 8.06 (d, 7 = 2.1 Hz, m/e 423 ridin-3- IH), 7.51 (d, 7 = 5.2 Hz, IH), 7.44 - 7.38 (m, 2H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 6.85 (dd, 7 = 8.7, 1.2 Hz, 2H), 4.82 (s, 4H), 4.28 - dihydro-2H- 4.17 (m, IH), 3.67 (s, 2H), 3.51 - 3.37 (m, 2H), 2.65 pyrrolo[3,4- (s, IH), 2.02 - 1.88 (m, IH), 1.79 - 1.65 (m, 2H), 1.63 c]pyridine-2- - 1.39 (m, 2H), 1.38 - 1.22 (m, IH), 0.98 (dd, 7 = 6.7, carboxamide 4.4 Hz, 3H), 0.90 - 0.76 (m, 3H)
1297 N-(4-{ [l-(3,3,3- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (s, (ESI(+)) trifluoropropanoyl)pi IH), 8.54 (d, 7 = 5.2 Hz, IH), 8.08 (m, IH), 7.52 (d, 7 m/e 449 peridin-3- = 5.1 Hz, IH), 7.42 (d, 7 = 8.9 Hz, 2H), 6.86 (d, 7 = (M+H)+ yl] o xy } phenyl) - 1 , 3 - 9.0 Hz, 2H), 4.82 (m, 4H), 4.26 (s, IH), 3.63 - 3.41
dihydro-2H- (m, 6H), 1.93 (d, 7 = 26.2 Hz, IH), 1.75 (m, 2H), 1.49 pyrrolo[3,4- (m, IH)
c]pyridine-2- carboxamide
1298 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (s, (ESI(+))
(cyclopropylacetyl)p IH), 8.53 (d, 7 = 5.2 Hz, IH), 8.06 (s, IH), 7.51 (d, 7 m/e 421 iperidin-3- = 5.3 Hz, IH), 7.48 - 7.35 (m, 2H), 6.92 - 6.79 (m, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.82 (s, 4H), 4.23 (m, IH), 3.42 - 3.13 (m, 4H), dihydro-2H- 2.27 (d, 7 = 33.4 Hz, 3H), 1.93 (d, 7 = 26.2 Hz, IH), pyrrolo[3,4- 1.72 (m, 2H), 1.46 (m, IH), 0.95 (m, IH), 0.43 (d, 7 =
c]pyridine-2- 8.0 Hz, 2H), 0.09 (m, 2H)
carboxamide
1299 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (s, (ESI(+))
(cyclobutylcarbonyl) IH), 8.53 (d, 7 = 5.1 Hz, IH), 8.07 (bs, IH), 7.50 (d, 7 m/e 421 piperidin-3- = 5.2 Hz, IH), 7.45 - 7.39 (m, 2H), 6.88 - 6.82 (m, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.82 (s, 4H), 4.27 - 4.15 (m, IH), 3.48 - 3.38 (m, dihydro-2H- 2H), 2.24 - 1.65 (m, 9H), 1.50 - 1.38 (m, IH)
pyrrolo[3,4- c]pyridine-2- carboxamide
1300 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (s, (ESI(+))
(cyclobutylacetyl)pi IH), 8.53 (d, 7 = 5.1 Hz, IH), 8.10 - 8.05 (m, IH), m/e 435 peridin-3- 7.51 (d, 7 = 5.2 Hz, IH), 7.42 (d, 7 = 7.7 Hz, IH), 6.89 (M+H)+ yl] o xy } phenyl) - 1 , 3 - - 6.82 (m, 2H), 4.82 (s, 4H), 4.51 - 3.84 (m, IH), 2.67 dihydro-2H- - 2.53 (m, IH), 2.30 (d, 7 = 7.4 Hz, IH), 2.11 - 1.91 pyrrolo[3,4- (m, 3H), 1.88 - 1.58 (m, 7H)
c]pyridine-2- carboxamide
1301 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (s, (ESI(+))
(cyclopentylcarbonyl IH), 8.53 (d, 7 = 5.2 Hz, IH), 8.07 (s, IH), 7.51 (d, 7 m/e 435
)piperidin-3- = 5.2 Hz, IH), 7.42 (dd, 7 = 9.0, 3.7 Hz, 2H), 6.86 (d, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 7 = 9.0 Hz, 2H), 4.82 (s, 4H), 4.45 - 3.57 (m, 5H),
dihydro-2H- 2.92 (s, 2H), 1.97 (s, IH), 1.67 (m, 12H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1302 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.65 (s, (ESI(+))
(cyclopentylacetyl)pi IH), 8.54 (d, 7 = 5.2 Hz, IH), 8.07 (s, IH), 7.52 (d, 7 m/e 449 peridin-3- = 5.2 Hz, IH), 7.49 - 7.35 (m, 2H), 6.92 - 6.79 (m, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 2H), 4.82 (s, 4H), 4.24 (s, IH), 3.46 (s, 4H), 2.36 - dihydro-2H- 2.07 (m, 3H), 1.93 (m,lH), 1.73 (m, 4H), 1.51 (dd, 7 =
pyrrolo[3,4- 22.2, 13.1 Hz, 5H), 1.13 (m, 2H)
c]pyridine-2- carboxamide
1303 N-[4-({ l-[(2S)- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (ESI(+)) tetrahydrofuran-2- (bs, IH), 8.53 (m, IH), 8.07 (bs, IH), 7.51 (d, 7 = 5.2 m/e 437 ylcarbonyl] piperidin Hz, IH), 7.44 - 7.38 (m, 3H), 6.87 (dd, 7 = 9.0, 3.3 (M+H)+ -3-yl } oxy)phenyl] - Hz, 3H), 4.82 (s, 4H), 4.64 - 4.50 (m, IH), 4.30 - 4.17 l,3-dihydro-2H- (m, IH), 3.99 - 3.87 (m, IH), 3.83 - 3.55 (m, 4H),
pyrrolo[3,4- 2.03 - 1.68 (m, 7H), 1.48 (m, IH)
c]pyridine-2- carboxamide
1304 N-[4-({ l-[(2R)- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (ESI(+)) tetrahydrofuran-2- (bs, IH), 8.54 (m, IH), 8.07 (bs, IH), 7.52 (d, 7 = 4.8 m/e 437 ylcarbonyl] piperidin Hz, IH), 7.44 - 7.38 (m, 3H), 6.91 - 6.83 (m, 3H), (M+H)+ -3-yl } oxy)phenyl] - 4.82 (bs, 4H), 4.64 - 4.49 (m, IH), 4.30 - 4.16 (m,
l,3-dihydro-2H- IH), 3.93 (s, IH), 3.43 - 3.20 (m, 3H), 2.05 - 1.75 (m, pyrrolo[3,4- 7H), 1.48 (s, IH)
c]pyridine-2- carboxamide
1305 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.62 (s, (ESI(+))
(tetrahydro-2H- IH), 8.52 (d, 7 = 5.1 Hz, IH), 8.06 (s, IH), 7.53 - 7.42 m/e 451 pyran-4- (m, 2H), 7.41 (s, IH), 6.91 - 6.79 (m, 2H), 4.81 (s, (M+H)+ ylcarbonyl)piperidin 4H), 4.26 (s, IH), 3.81 (m, 3H), 3.45 (s, 2H), 2.76 (s,
-3 -yl] oxy } phenyl) - 2H), 2.14 (m, 2H), 1.88 - 1.42 (m, 7H)
l,3-dihydro-2H- pyrrolo[3,4- c]pyridine-2- carboxamide
1306 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.62 (s, (ESI(+))
(tetrahydro-2H- IH), 8.52 (d, 7 = 5.1 Hz, IH), 8.06 (s, IH), 7.47 (d, 7 m/e 451 pyran-2- = 5.2 Hz, IH), 7.42 (dd, 7 = 9.1, 2.6 Hz, 2H), 6.86 (M+H)+ ylcarbonyl)piperidin (dd, 7 = 9.0, 2.1 Hz, 2H), 4.81 (s, 4H), 4.08 (m, 3H),
-3 -yl] oxy } phenyl) - 3.93 - 3.54 (m, 3H), 3.28 - 3.13 (m, 2H), 2.00 (s, IH), l,3-dihydro-2H- 1.85 - 1.36 (m, 9H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1307 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (s, (ESI(+))
(tetrahydro-2H- IH), 8.54 (d, 7 = 5.2 Hz, IH), 8.07 (s, IH), 7.51 (d, 7 m/e 465 pyran-4- = 5.1 Hz, IH), 7.42 (d, 7 = 8.9 Hz, 2H), 6.85 (d, 7 = (M+H)+ ylacetyl)piperidin-3- 9.0 Hz, 2H), 4.24 (s, 2H), 3.32 (dd, 7 = 50.2, 38.3 Hz, yl] o xy } phenyl) - 1 , 3 - 6H), 2.20 (m, 2H), 1.92 (m, 2H), 1.73 (m, 2H), 1.56
dihydro-2H- (m, 2H), 1.46 (m, IH), 1.20 (m, 2H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1308 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.63 (s, (ESI(+)) (tetrahydrofuran-2- IH), 8.52 (d, 7 = 5.2 Hz, IH), 8.06 (s, IH), 7.49 (d, 7 m/e 451 ylacetyl)piperidin-3- = 5.2 Hz, 1H), 7.42 (d, J = 8.8 Hz, 2H), 6.86 (d, 7 = (M+H)+ y 1] o xy } phenyl) - 1 , 3 - 9.0 Hz, 2H), 4.81 (s, 5H), 4.37 - 4.03 (m, 2H), 3.71 (s, dihydro-2H- 2H), 3.63 - 3.50 (m, 3H), 2.61 (m, 2H), 2.44 - 2.25
pyrrolo[3,4- (m, 1H), 1.96 (m, 2H), 1.87 - 1.63 (m, 4H), 1.47 (m,
c]pyridine-2- 2H)
carboxamide
1309 N-(4-{ [l- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.64 (s, (ESI(+))
(tetrahydrofuran-3- 1H), 8.54 (d, 7 = 5.2 Hz, 1H), 8.07 (s, 1H), 7.51 (d, 7 m/e 451 ylacetyl)piperidin-3- = 5.2 Hz, 1H), 7.42 (d, 7 = 8.9 Hz, 2H), 6.89 - 6.76 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (m, 2H), 4.82 (s, 5H), 4.27 (s, 1H), 3.67 - 3.17 (m,
dihydro-2H- 11H), 2.34 (d, 7 = 26.3 Hz, 3H), 1.93 (d, 7 = 29.4 Hz,
pyrrolo[3,4- 3H), 1.73 (s, 3H), 1.47 (s, 3H)
c]pyridine-2- carboxamide
1347 N-(4-{ [l-(5-oxo-L- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) prolyl)piperidin-4- ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.40 (d, m/e 450 yl] o xy } phenyl) - 1 , 3 - 7=8.54 Hz, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.79 (d, (M+H)+ dihydro-2H- 7=7.63 Hz, 4 H) 4.45 - 4.58 (m, 2 H) 3.75 (s, 2 H)
pyrrolo[3,4- 3.34 - 3.42 (m, 4 H) 2.30 - 2.43 (m, 1 H) 2.10 - 2.21
c]pyridine-2- (m, 2 H) 1.94 (d, 7=5.80 Hz, 1 H) 1.54 - 1.69 (m, 2 H) carboxamide
1386 N-(4-{ [l-(5-oxo-L- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) prolyl)azetidin-3- ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.38 - 7.48 m/e 421 yl] o xy } phenyl) - 1 , 3 - (m, 3 H) 6.75 - 6.83 (m, 2 H) 4.98 - 5.06 (m, 1 H) 4.79 (M+H)+ dihydro-2H- (d, 7=7.93 Hz, 4 H) 4.29 - 4.72 (m, 2 H) 4.18 (dd,
pyrrolo[3,4- 7=8.39, 4.73 Hz, 1 H) 3.64 - 4.12 (m, 2 H) 2.06 - 2.41
c]pyridine-2- (m, 3 H) 1.90 - 2.06 (m, 1 H)
carboxamide
1387 N-{4-[(l- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) propanoylazetidin-3- ppm 8.57 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.38 - 7.46 m/e 367 yl)o xy] phenyl } - 1 , 3 - (m, 3 H) 6.74 - 6.82 (m, 2 H) 4.94 - 5.03 (m, 1 H) 4.79 (M+H)+ dihydro-2H- (d, 7=7.02 Hz, 4 H) 4.35 (s, 2 H) 3.90 (s, 2 H) 2.10 (q, pyrrolo[3,4- 7=7.43 Hz, 2 H) 1.00 (t, 7=7.48 Hz, 3 H)
c]pyridine-2- carboxamide
1388 N-(4-{ [l-(2,2- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) dimethylbutanoyl)az ppm 8.57 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.39 - 7.46 m/e 409 etidin-3- (m, 3 H) 6.78 (d, 7=8.85 Hz, 2 H) 4.90 - 5.02 (m, 1 H) (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4.79 (d, 7=7.93 Hz, 4 H) 4.51 (s, 2 H) 4.01 (d, 7=8.54
dihydro-2H- Hz, 2 H) 1.49 (q, 7=7.32 Hz, 2 H) 1.09 (s, 6 H) 0.81 (t, pyrrolo[3,4- 7=7.48 Hz, 3 H)
c]pyridine-2- carboxamide
1389 N-(4-{ [l-(2- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) ethylbutanoyl) azetidi ppm 8.57 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.37 - 7.47 m/e 409 n-3 -yl] oxy } phenyl) - (m, 3 H) 6.79 (d, 7=8.85 Hz, 2 H) 4.95 - 5.03 (m, 1 H) (M+H)+ l,3-dihydro-2H- 4.79 (d, 7=7.93 Hz, 4 H) 4.44 (s, 2 H) 3.95 (s, 2 H)
pyrrolo[3,4- 2.08 - 2.22 (m, 1 H) 1.32 - 1.55 (m, 4 H) 0.83 (t,
c]pyridine-2- 7=7.32 Hz, 6 H)
carboxamide
1390 N-(4-{ [l-(pent-4- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) ynoyl) azetidin- 3 - ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.34 - 7.49 m/e 391 yl] o xy } phenyl) - 1 , 3 - (m, 3 H) 6.78 (d, 7=8.85 Hz, 2 H) 4.92 - 5.06 (m, 1 H) (M+H)+ dihydro-2H- 4.79 (d, 7=7.93 Hz, 4 H) 4.42 (d, 7=78.13 Hz, 2 H) pyrrolo[3,4- 3.66 - 4.19 (m, 2 H) 2.54 (t, 7=2.44 Hz, 1 H) 2.27 - c]pyridine-2- 2.43 (m, 4 H)
carboxamide
1391 N-(4-{ [l-(furan-2- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) ylcarbonyl) azetidin- ppm 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.77 (s, 1 m/e 405
3-yl] oxy jphenyl)- H) 7.37 - 7.48 (m, 3 H) 7.04 (d, 7=3.66 Hz, 1 H) 6.81 (M+H)+ l,3-dihydro-2H- (d, 7=8.85 Hz, 2 H) 6.57 - 6.63 (m, 1 H) 5.01 - 5.14
pyrrolo[3,4- (m, 1 H) 4.79 (d, 7=8.24 Hz, 4 H) 4.67 (s, 2 H) 4.17
c]pyridine-2- (s, 2 H)
carboxamide
1392 N-(4-{ [l-(furan-3- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) ylcarbonyl) azetidin- ppm 8.57 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 8.07 (s, 1 m/e 405
3-yl] oxy jphenyl)- H) 7.67 (s, 1 H) 7.38 - 7.47 (m, 3 H) 6.80 (d, 7=8.85 (M+H)+ l,3-dihydro-2H- Hz, 2 H) 6.72 (s, 1 H) 5.03 - 5.11 (m, 1 H) 4.79 (d,
pyrrolo[3,4- 7=7.63 Hz, 4 H) 4.60 (s, 2 H) 4.12 (s, 2 H)
c]pyridine-2- carboxamide
1393 N-(4-{ [l-(thiophen- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) 3- ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.97 (d, m/e 421 ylcarbonyl) azetidin- 7=1.83 Hz, 1 H) 7.55 (dd, 7=5.04, 2.90 Hz, 1 H) 7.35 - (M+H)+
3-yl] oxy jphenyl)- 7.46 (m, 4 H) 6.80 (d, 7=8.85 Hz, 2 H) 5.01 - 5.11 (m, l,3-dihydro-2H- 1 H) 4.79 (d, 7=7.93 Hz, 4 H) 4.62 (s, 2 H) 4.16 (s, 2
pyrrolo[3,4- H)
c]pyridine-2- carboxamide
1394 N-(4-{ [l-(lH-pyrrol- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) 2- ppm 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.37 - 7.48 m/e 404 ylcarbonyl) azetidin- (m, 3 H) 6.93 (s, 1 H) 6.81 (d, 7=8.85 Hz, 2 H) 6.51 (M+H)+
3-yl] oxy jphenyl)- (d, 7=3.36 Hz, 1 H) 6.14 - 6.18 (m, 1 H) 5.02 - 5.14
l,3-dihydro-2H- (m, 1 H) 4.79 (d, 7=7.93 Hz, 4 H) 4.57 - 4.66 (m, 2 H) pyrrolo[3,4- 4.13 (d, 7=7.93 Hz, 2 H)
c]pyridine-2- carboxamide
1395 N-(4-{ [l-(pyrimidin- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) 4- ppm 9.09 (s, 1 H) 8.75 (d, 7=2.14 Hz, 1 H) 8.66 (s, 1 m/e 417 ylcarbonyl) azetidin- H) 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.37 - 7.47 (M+H)+
3-yl] oxy jphenyl)- (m, 3 H) 6.81 (d, 7=8.85 Hz, 2 H) 5.06 - 5.13 (m, 1 H) l,3-dihydro-2H- 4.92 - 5.04 (m, 1 H) 4.79 (d, 7=7.63 Hz, 4 H) 4.50 (s,
pyrrolo[3,4- 2 H) 4.09 (s, 1 H)
c]pyridine-2- carboxamide
1396 N-[4-({ l-[(5- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) methylpyrazin-2- ppm 8.96 (s, 1 H) 8.58 (s, 1 H) 8.54 (s, 1 H) 8.48 (d, m/e 431 yl)carbonyl] azetidin- 7=4.88 Hz, 1 H) 7.38 - 7.47 (m, 3 H) 6.80 (d, 7=8.85 (M+H)+ 3 -yl } oxy)phenyl] - Hz, 2 H) 5.04 - 5.13 (m, 1 H) 4.89 - 5.02 (m, 1 H)
l,3-dihydro-2H- 4.79 (d, 7=7.63 Hz, 4 H) 4.48 (s, 2 H) 4.06 (s, 1 H)
pyrrolo[3,4- 2.57 (s, 3 H)
c]pyridine-2- carboxamide
1397 N-(4-{ [l-(N,N- ¾ NMR (400 MHz, DMSO- Deuterium Oxide, (APCI(+)) dimethylglycyl)azeti Temp=90°C) δ ppm 8.57-8.59 (bs, 1H), 8.48 (dd, 7 = m/e 396 din-3- 4.9, 1.8 Hz, 1H), 7.43-7.47 (m, 2H), 7.41 (d, 7 = 6.7 (M+H)+ yl] o xy } phenyl) - 1 , 3 - Hz, 1H), 6.80-6.83 (m, 2H), 5.08-5.16 (m, 1H), 4.82
dihydro-2H- (s, 2H), 4.79 (s, 2H), 4.67-4.74 (m, 2H), 4.30 (dd, 7 = pyrrolo[3,4- 10.1, 4.1 Hz, 2H), 2.91 (s, 8H)
c]pyridine-2- carboxamide
1398 N-(4-{ [l-(N,N- ¾ NMR (400 MHz, DMSO-i¾/Deuterium Oxide, (APCI(+)) dimethyl-beta- Temp=90°C) δ ppm 8.57 (s, 1H), 8.48 (d, J = 5.2 Hz, m/e 410 alanyl) azetidin-3 - 1H), 7.44-7.48 (m, 2H), 7.40 (d, 7 = 4.6 Hz, 1H), (M+H)+ yl] o xy } phenyl) - 1 , 3 - 6.80-6.84 (m, 2H), 5.09-5.16 (m, 1H), 4.83 (s, 2H),
dihydro-2H- 4.79 (s, 2H), 4.70 (ddd, 7 = 10.4, 6.6, 1.2 Hz, 2H),
pyrrolo[3,4- 4.30 (ddd, 7 = 10.4, 4.1, 1.2 Hz, 2H), 2.91 (s, 6H),
c]pyridine-2- 2.50 (t, 7 = 7.3 Hz, 2H), 2.23 (t, 7 = 7.2 Hz, 2H)
carboxamide
1399 N-(4-{ [l-(pyrrolidin- ¾ NMR (400 MHz, DMSO- Deuterium Oxide, (APCI(+))
1 -ylacetyl)azetidin- Temp=90°C) 8 ppm 8.58 (s, 1H), 8.48 (dd, 7 = 5.2, 1.8 m/e 422
3-yl] oxy jphenyl)- Hz, 1H), 7.43-7.47 (m, 2H), 7.40 (d, 7 = 5.2 Hz, 1H), (M+H)+ l,3-dihydro-2H- 6.80-6.84 (m, 2H), 5.09-5.16 (m, 1H), 4.82 (s, 2H),
pyrrolo[3,4- 4.79 (s, 2H), 4.70 (ddd, 7 = 10.2, 6.4, 1.1 Hz, 2H),
c]pyridine-2- 4.30 (ddd, 7 = 10.3, 4.2, 1.1 Hz, 2H), 3.18 (s, 2H),
carboxamide 2.55-2.62 (m, 4H), 1.68-1.75 (m, 4H)
1400 N-[4-({ l-[3- ¾ NMR (400 MHz, DMSO- Deuterium Oxide, (APCI(+)) (pyrrolidin-1- Temp=90°C) δ ppm 8.57-8.58 (bs, 1H), 8.48 (dd, 7 = m/e 436 yl)prop anoyl] azetidi 5.0, 2.0 Hz, 1H), 7.41-7.45 (m, 2H), 7.40 (d, 7 = 4.9 (M+H)+ n-3-yl } oxy)phenyl] - Hz, 1H), 6.76-6.80 (m, 2H), 4.94-5.01 (m, 1H), 4.82
l,3-dihydro-2H- (s, 2H), 4.79 (s, 2H), 4.19-4.64 (m, 2H), 3.70-4.17 (m, pyrrolo[3,4- 2H), 2.66 (t, 7 = 7.3 Hz, 2H), 2.44-2.50 (m, 4H), 2.27
c]pyridine-2- (t, 7 = 7.3 Hz, 2H), 1.65-1.71 (m, 4H)
carboxamide
1401 N-[4-({ l-[3- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) (piperidin-1- ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.35 - 7.48 m/e 450 yl)prop anoyl] azetidi (m, 3 H) 6.74 - 6.83 (m, 2 H) 4.92 - 5.02 (m, 1 H) 4.79 (M+H)+ n-3-yl } oxy)phenyl] - (d, 7=7.93 Hz, 4 H) 4.18 - 4.71 (m, 2 H) 3.94 (d,
l,3-dihydro-2H- 7=92.77 Hz, 2 H) 2.53 - 2.58 (m, 2 H) 2.32 - 2.40 (m,
pyrrolo[3,4- 4 H) 2.24 (t, 7=7.17 Hz, 2 H) 1.44 - 1.54 (m, 4 H) 1.33 c]pyridine-2- - 1.41 (m, 2 H)
carboxamide
1402 N-[4-({ l-[(4- ¾ NMR (400 MHz, DMSO- Deuterium Oxide, (APCI(+)) methylpiperazin- 1 - Temp=90°C) δ ppm 8.58 (s, 1H), 8.48 (dd, 7 = 5.0, 2.0 m/e 451 yl)acetyl]azetidin-3- Hz, 1H), 7.41-7.45 (m, 2H), 7.40 (d, 7 = 5.2 Hz, 1H), (M+H)+ yl } oxy)phenyl] -1,3- 6.75-6.80 (m, 2H), 5.08-5.17 (m, 1H), 4.82 (s, 2H),
dihydro-2H- 4.79 (s, 2H), 4.70 (ddd, 7 = 10.0, 6.3, 1.3 Hz, 2H),
pyrrolo[3,4- 4.30 (ddd, 7 = 10.0, 4.0, 1.0 Hz, 2H), 3.00 (s, 2H),
c]pyridine-2- 2.41-2.48 (m, 4H), 2.30-2.37 (m, 4H), 2.15 (s, 3H)
carboxamide
1403 N-[4-({ l-[3-(4- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) methylpiperazin- 1 - ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.38 - 7.48 m/e 456 yl)prop anoyl] azetidi (m, 3 H) 6.78 (d, 7=9.16 Hz, 2 H) 4.93 - 5.01 (m, 1 H) (M+H)+ n-3-yl } oxy)phenyl] - 4.79 (d, 7=7.93 Hz, 4 H) 4.19 - 4.64 (m, 2 H) 3.94 (d,
l,3-dihydro-2H- 7=87.28 Hz, 2 H) 2.53 - 2.58 (m, 2 H) 2.36 - 2.43 (m,
pyrrolo[3,4- 4 H) 2.29 - 2.35 (m, 4 H) 2.24 (t, 7=7.17 Hz, 2 H) 2.15 c]pyridine-2- (s, 3 H)
carboxamide
1423 N-[4-({ l-[(2S)-2- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (ESI(+)) methylbutanoyl]pipe (d, 7 = 5.0 Hz, 1H), 8.27 (s, 1H), 7.51 - 7.34 (m, 3H), m/e 423 ridin-4- 6.90 (d, 7 = 9.0 Hz, 2H), 4.78 (d, 7 = 4.0 Hz, 4H), 4.60 (M+H)+ yl } oxy)phenyl] -1,3- - 4.44 (m, 1H), 3.84 (d, 7 = 39.0 Hz, 2H), 3.46 - 3.12 dihydro-2H- (m, 2H), 2.73 (dd, J = 13.4, 6.8 Hz, 1H), 1.99 (s, 2H), pyrrolo[3,4- 1.55 (dt, 7 = 21.7, 7.3 Hz, 3H), 1.42 - 1.21 (m, 1H),
c]pyridine-2- 0.97 (t, 7 = 5.7 Hz, 3H), 0.81 (t, 7 = 7.4 Hz, 3H)
carboxamide
1424 N-[4-({ l-[(2S)- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (ESI(+)) tetrahydrofuran-2- (d, 7 = 5.0 Hz, 1H), 8.28 (s, 1H), 7.46 - 7.39 (m, 3H), m/e 437 ylcarbonyl] piperidin 6.94 - 6.87 (m, 2H), 4.86 - 4.74 (m, 4H), 4.67 (t, 7 = (M+H)+ -4-yl } oxy)phenyl] - 6.6 Hz, 1H), 4.57 - 4.46 (m, 1H), 3.93 - 3.67 (m, 4H), l,3-dihydro-2H- 3.31 (s, 2H), 2.12 - 1.77 (m, 6H), 1.65 - 1.39 (m, 2H) pyrrolo[3,4- c]pyridine-2- carboxamide
1425 N-[4-({ l-[(2R)- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (ESI(+)) tetrahydrofuran-2- (d, 7 = 5.0 Hz, 1H), 8.27 (s, 1H), 7.53 - 7.33 (m, 3H), m/e 437 ylcarbonyl] piperidin 6.90 (d, 7 = 9.0 Hz, 2H), 4.78 (d, 7 = 4.0 Hz, 4H), 4.73 (M+H)+ -4-yl } oxy)phenyl] - - 4.60 (m, 1H), 4.52 (s, 1H), 3.93 - 3.63 (m, 4H), 3.49 l,3-dihydro-2H- - 3.07 (m, 2H), 2.11 - 1.72 (m, 6H), 1.66 - 1.40 (m,
pyrrolo[3,4- 2H)
c]pyridine-2- carboxamide
1426 N-[4-({ l-[(4,4- ¾ NMR (400 MHz, DMSO, Temp = 90 °C) δ 8.57 (s, (ESI(+)) difluorocyclohexyl)c 1H), 8.47 (d, 7 = 5.0 Hz, 1H), 8.05 (d, 7 = 8.0 Hz, m/e 457 arbonyl]azetidin-3- 1H), 7.48 - 7.39 (m, 2H), 7.37 (d, 7 = 4.8 Hz, 1H), (M+H)+ yl } oxy)phenyl] -1,3- 6.86 - 6.60 (m, 2H), 4.96 (m, 1H), 4.78 (d, 7 = 8.8 Hz, dihydro-2H- 5H), 4.19 (m, 2H), 3.74 (m, 2H), 3.22 (d, 7 = 6.2 Hz,
pyrrolo[3,4- 1H), 2.42 (t, 7 = 10.6 Hz, 1H), 2.26 (t, 7 = 6.9 Hz,
c]pyridine-2- 1H), 2.04 (d, 7 = 10.0 Hz, 2H), 1.81 (ddd, 7 = 26.3,
carboxamide 15.5, 8.4 Hz, 3H), 1.68 - 1.49 (m, 2H)
1427 N-(4-{ [l-(5-oxo-D- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) prolyl)piperidin-4- ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.40 (d, m/e 450 yl] o xy } phenyl) - 1 , 3 - 7=8.54 Hz, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.79 (d, (M+H)+ dihydro-2H- 7=7.63 Hz, 4 H) 4.46 - 4.60 (m, 2 H) 3.75 (s, 2 H)
pyrrolo[3,4- 3.34 - 3.41 (m, 2 H) 2.30 - 2.41 (m, 1 H) 2.10 - 2.23
c]pyridine-2- (m, 2 H) 1.92 - 2.05 (m, 3 H) 1.56 - 1.74 (m, 2 H)
carboxamide
1428 N-(4-{ [l-(2,2- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) dime thy lprop ano yl)p ppm 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.36 - 7.44 m/e 423 iperidin-4- (m, 3 H) 6.89 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=7.32 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4 H) 4.43 - 4.53 (m, 1 H) 3.80 - 3.93 (m, 2 H) 3.34 - dihydro-2H- 3.42 (m, 2 H) 1.94 - 1.99 (m, 7=3.36 Hz, 2 H) 1.50 - pyrrolo[3,4- 1.68 (m, 2 H) 1.22 (s, 9 H)
c]pyridine-2- carboxamide
1429 N-(4-{ [l-(2- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) methylpentanoyl)pip ppm 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.40 (d, m/e 437 eridin-4- 7=8.85 Hz, 3 H) 6.89 (d, 7=8.85 Hz, 2 H) 4.79 (d, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 7=7.32 Hz, 4 H) 4.45 - 4.54 (m, 1 H) 3.81 (dd,
dihydro-2H- 7=11.14, 5.34 Hz, 2 H) 3.35 (s, 2 H) 2.75 - 2.84 (m, 1
pyrrolo[3,4- H) 1.93 - 1.98 (m, 2 H) 1.49 - 1.64 (m, 3 H) 1.19 - c]pyridine-2- 1.35 (m, 3 H) 1.01 (d, 7=6.71 Hz, 3 H) 0.86 (t, 7=7.02
carboxamide Hz, 3 H)
1430 N-(4-{ [l-(2- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) ethylbutanoyl)piperi ppm 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.40 (d, m/e 437 din-4- 7=9.16 Hz, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.79 (d, (M+H)+ y 1] o xy } phenyl) - 1 , 3 - 7=7.63 Hz, 4 H) 4.46 - 4.56 (m, 7=11.22, 7.40, 3.66
dihydro-2H- Hz, 1 H) 3.80 - 3.92 (m, 2 H) 3.35 - 3.43 (m, 2 H)
pyrrolo[3,4- 2.58 - 2.68 (m, 1 H) 1.87 - 1.95 (m, 2 H) 1.47 - 1.64
c]pyridine-2- (m, 4 H) 1.34 - 1.46 (m, 2 H) 0.82 (t, 7=7.48 Hz, 6 H)
carboxamide
1431 N-(4-{ [l-(lH-pyrrol- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) 2- ppm 8.57 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.37 - 7.46 m/e 432 ylcarbonyl)piperidin (m, 3 H) 6.85 - 6.95 (m, 3 H) 6.49 (d, 7=3.05 Hz, 1 H) (M+H)+
-4-yl] oxy } phenyl) - 6.13 (t, 7=2.90 Hz, 1 H) 4.79 (d, 7=7.93 Hz, 4 H) 4.47
l,3-dihydro-2H- - 4.60 (m, 1 H) 3.93 - 4.09 (m, 2 H) 3.49 - 3.59 (m, 2
pyrrolo[3,4- H) 1.95 - 2.03 (m, 2 H) 1.56 - 1.74 (m, 2 H)
c]pyridine-2- carboxamide
1432 N-(4-{ [l-(l,2- ¾ NMR (400 MHz, Solvent) δ ppm 8.57 (s, 1 H) 8.47 (APCI(+)) oxazol-5- (d, 7=4.88 Hz, 1 H) 7.36 - 7.44 (m, 3 H) 6.89 (d, m/e 434 ylcarbonyl)piperidin 7=8.54 Hz, 2 H) 4.79 (d, 7=7.93 Hz, 4 H) 3.44 - 4.62 (M+H)+
-4-yl] oxy } phenyl) - (m, 4 H) 1.79 - 1.89 (m, 2 H) 1.40 - 1.80 (m, 3 H)
l,3-dihydro-2H- pyrrolo[3,4- c]pyridine-2- carboxamide
1433 N-(4-{ [l-(pyridin-3- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) ylcarbonyl)piperidin ppm 8.62 (d, 7=4.58 Hz, 1 H) 8.58 (d, 7=7.32 Hz, 2 H) m/e 444
-4-yl] oxy } phenyl) - 8.47 (d, 7=5.19 Hz, 1 H) 7.82 (d, 7=7.93 Hz, 1 H) 7.47 (M+H)+ l,3-dihydro-2H- (dd, 7=7.63, 4.88 Hz, 1 H) 7.40 (d, 7=8.54 Hz, 3 H)
pyrrolo[3,4- 6.91 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=7.63 Hz, 4 H) 4.50 c]pyridine-2- - 4.58 (m, 1 H) 3.75 (s, 2 H) 3.38 - 3.50 (m, 7=8.85
carboxamide Hz, 2 H) 1.93 - 2.05 (m, 2 H) 1.62 - 1.76 (m, 2 H)
1434 N-(4-{ [l-(pyridazin- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) 3- ppm 9.26 (dd, 7=4.58, 2.14 Hz, 1 H) 8.58 (s, 1 H) 8.49 m/e 445 ylcarbonyl)piperidin (d, 7=4.88 Hz, 1 H) 7.76 - 7.85 (m, 2 H) 7.37 - 7.45 (M+H)+
-4-yl] oxy } phenyl) - (m, 3 H) 6.91 (t, 7=9.16 Hz, 2 H) 4.80 (d, 7=6.10 Hz,
l,3-dihydro-2H- 4 H) 4.48 - 4.63 (m, 1 H) 3.99 (s, 2 H) 3.60 (s, 2 H)
pyrrolo[3,4- 1.95 - 2.14 (m, 2 H) 1.72 (s, 2 H)
c]pyridine-2- carboxamide
1435 N-(4-{ [l-(pyrazin-2- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) ylcarbonyl)piperidin ppm 9.20 (s, 1 H) 8.93 (d, 7=5.19 Hz, 1 H) 8.57 (s, 1 m/e 445
-4-yl] oxy } phenyl) - H) 8.47 (d, 7=4.88 Hz, 1 H) 7.60 - 7.65 (m, 1 H) 7.36 (M+H)+ l,3-dihydro-2H- - 7.44 (m, 3 H) 6.87 - 6.94 (m, 2 H) 4.79 (d, 7=7.63
pyrrolo[3,4- Hz, 4 H) 4.47 - 4.62 (m, 1 H) 3.94 (s, 2 H) 3.55 (s, 2
c]pyridine-2- H) 1.93 - 2.11 (m, 2 H) 1.61 - 1.78 (m, 7=15.87 Hz, 2
carboxamide H)
1436 N-(4-{ [l-(pyrimidin- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) 4- ppm 8.40 - 8.87 (m, 5 H) 7.33 - 7.47 (m, 3 H) 6.91 (d, m/e 445 ylcarbonyl)piperidin 7=8.85 Hz, 2 H) 4.79 (d, 7=7.93 Hz, 4 H) 4.48 - 4.63 (M+H)+
-4-yl] oxy } phenyl) - (m, 1 H) 3.45 - 4.22 (m, 4 H) 1.94 - 2.12 (m, 2 H) 1.56 l,3-dihydro-2H- - 1.79 (m, 2 H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1437 N-[4-({ l-[(5- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) methylpyrazin-2- ppm 8.66 (s, 1 H) 8.57 (s, 1 H) 8.52 (s, 1 H) 8.48 (d, m/e 459 yl)carbonyl]piperidi 7=4.88 Hz, 1 H) 7.40 (d, 7=8.54 Hz, 3 H) 6.91 (d, (M+H)+ n-4-yl } oxy)phenyl] - 7=9.16 Hz, 2 H) 4.79 (d, 7=7.63 Hz, 4 H) 4.51 - 4.60
l,3-dihydro-2H- (m, 1 H) 3.63 - 4.07 (m, 2 H) 3.39 - 3.62 (m, 2 H) 2.55 pyrrolo[3,4- (s, 3 H) 1.93 - 2.06 (m, 2 H) 1.62 - 1.78 (m, 7=10.38
c]pyridine-2- Hz, 2 H)
carboxamide
1438 N-[4-({ l-[3- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+))
(piperidin-1- ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.33 - 7.45 m/e 478 yl)propanoyl]piperid (m, 3 H) 6.89 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=7.93 Hz, (M+H)+ in-4-yl } oxy)phenyl] - 4 H) 4.43 - 4.52 (m, 1 H) 3.66 - 3.92 (m, 2 H) 3.34 - l,3-dihydro-2H- 3.40 (m, 2 H) 2.55 - 2.62 (m, 7=7.02, 7.02 Hz, 2 H)
pyrrolo[3,4- 2.46 - 2.50 (m, 2 H) 2.37 - 2.43 (m, 4 H) 1.91 - 2.00
c]pyridine-2- (m, 2 H) 1.55 - 1.68 (m, 2 H) 1.45 - 1.55 (m, 4 H) 1.33 carboxamide - 1.42 (m, 2 H)
1439 N-(4-{ [l- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+))
(morpholin-4- ppm 8.57 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.34 - 7.48 m/e 466 ylacetyl)piperidin-4- (m, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=7.63 Hz, (M+H)+ yl] o xy } phenyl) - 1 , 3 - 4 H) 4.40 - 4.59 (m, 1 H) 3.72 - 3.91 (m, 2 H) 3.53 - dihydro-2H- 3.64 (m, 4 H) 3.35 - 3.45 (m, 2 H) 3.16 (s, 2 H) 2.39 - pyrrolo[3,4- 2.47 (m, 4 H) 1.90 - 2.01 (m, 2 H) 1.50 - 1.68 (m, 2 H) c]pyridine-2- carboxamide
1440 N-[4-({ l-[3-(4- ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ (APCI(+)) methylpiperazin- 1 - ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.36 - 7.44 m/e 493 yl)propanoyl]piperid (m, 3 H) 6.89 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=7.93 Hz, (M+H)+ in-4-yl } oxy)phenyl] - 4 H) 4.40 - 4.60 (m, 1 H) 3.69 - 3.85 (m, 2 H) 3.36 - l,3-dihydro-2H- 3.50 (m, 2 H) 2.55 - 2.63 (m, 2 H) 2.46 - 2.50 (m, 2 H) pyrrolo[3,4- 2.40 - 2.45 (m, 4 H) 2.30 - 2.36 (m, 4 H) 2.16 (s, 3 H)
c]pyridine-2- 1.91 - 2.00 (m, 2 H) 1.52 - 1.67 (m, 2 H)
carboxamide
1532 N-(4-{ [(3R)-l-(3- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.49 (ESI(+)) methylbutanoyl)pyrr (d, 7 = 5.0 Hz, 1H), 8.28 (s, 1H), 7.49 - 7.36 (m, 3H), m/e 409 olidin-3- 6.95 - 6.79 (m, 2H), 4.96 (d, 7 = 21.2 Hz, 1H), 4.78 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (d, 7 = 4.0 Hz, 5H), 3.81 - 3.44 (m, 4H), 2.21 - 1.84
dihydro-2H- (m, 6H), 0.99 - 0.79 (m, 6H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1533 N-(4-{ [(3R)-l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.49 (ESI(+))
(cyclobutylcarbonyl) (d, 7 = 5.0 Hz, 1H), 8.28 (s, 1H), 7.53 - 7.38 (m, 3H), m/e 407 pyrrolidin-3- 6.96 - 6.81 (m, 2H), 5.04 - 4.85 (m, 1H), 4.78 (d, 7 = (M+H)+ yl] o xy } phenyl) - 1 , 3 - 3.9 Hz, 4H), 3.72 - 3.07 (m, 5H), 2.24 - 1.56 (m, 8H) dihydro-2H- pyrrolo[3,4- c]pyridine-2- carboxamide
1534 N-[4-({(3R)-l-[(2R)- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (ESI(+)) tetrahydrofuran-2- (d, 7 = 5.0 Hz, 1H), 8.29 (s, 1H), 7.48 - 7.43 (m, 2H), m/e 423 ylcarbonyl] pyrrolidi 7.45 - 7.39 (m, 2H), 6.92 - 6.83 (m, 2H), 5.05 - 4.90 (M+H)+ n-3-yl } oxy)phenyl] - (m, 1H), 4.82 - 4.75 (m, 4H), 4.59 - 4.42 (m, 1H),
l,3-dihydro-2H- 3.89 - 3.42 (m, 5H), 2.25 - 1.68 (m, 6H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1535 N-[4-({(3R)-l-[(2S)- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (ESI(+)) tetrahydrofuran-2- (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.45 - 7.39 (m, 2H), m/e 423 ylcarbonyl] pyrrolidi 6.93 - 6.83 (m, 2H), 5.06 - 4.90 (m, IH), 4.82 - 4.75 (M+H)+ n-3-yl } oxy)phenyl] - (m, 4H), 4.60 - 4.42 (m, IH), 3.85 - 3.63 (m, 3H),
l ,3-dihydro-2H- 3.63 - 3.41 (m, 2H), 2.30 - 1.71 (m, 6H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1536 N-(4-{ [(3R)- l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+))
(cyclopropylacetyl)p (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.48 - 7.40 (m, 3H), m/e 407 yrrolidin-3- 6.92 - 6.82 (m, 2H), 5.03 - 4.90 (m, IH), 4.81 - 4.75 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (m, 4H), 3.79 - 3.43 (m, 2H), 2.32 - 1.95 (m, 5H),
dihydro-2H- 1.05 - 0.88 (m, IH), 0.49 - 0.36 (m, 2H), 0.20 - 0.07 pyrrolo[3,4- (m, 2H)
c]pyridine-2- carboxamide
1537 N-(4-{ [(3S)-l-(3- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+)) methylbutanoyl)pyrr (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.49 - 7.39 (m, 3H), m/e 409 olidin-3- 6.92 - 6.81 (m, 2H), 5.04 - 4.89 (m, IH), 4.81 - 4.75 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (m, 4H), 3.66 - 3.42 (m, 4H), 2.25 - 1.90 (m, 5H),
dihydro-2H- 0.96 - 0.82 (m, 6H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1538 N-(4-{ [(3S)-l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+))
(cyclobutylcarbonyl) (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.48 - 7.40 (m, 3H), m/e 407 pyrrolidin-3- 6.91 - 6.81 (m, 2H), 5.02 - 4.89 (m, IH), 4.81 - 4.75 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (m, 4H), 3.32 (s, 5H), 2.27 - 1.65 (m, 8H)
dihydro-2H- pyrrolo[3,4- c]pyridine-2- carboxamide
1539 N-[4-({ (3S)-l-[(2R)- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+)) tetrahydrofuran-2- (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.48 - 7.41 (m, 3H), m/e 423 ylcarbonyl] pyrrolidi 7.43 (d, J = 5.4 Hz, 2H), 6.93 - 6.82 (m, 2H), 5.05 - (M+H)+ n-3-yl } oxy)phenyl] - 4.91 (m, IH), 4.81 - 4.75 (m, 4H), 4.60 - 4.42 (m,
l,3-dihydro-2H- IH), 3.89 - 3.64 (m, 4H), 3.65 - 3.43 (m, 2H), 2.26 - pyrrolo[3,4- 1.73 (m, 6H)
c]pyridine-2- carboxamide
1540 N-[4-({ (3S)-l-[(2S)- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+)) tetrahydrofuran-2- (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.48 - 7.40 (m, 3H), m/e 423 ylcarbonyl] pyrrolidi 6.93 - 6.83 (m, 2H), 5.05 - 4.91 (m, IH), 4.81 - 4.75 (M+H)+ n-3-yl } oxy)phenyl] - (m, 3H), 4.59 - 4.42 (m, IH), 3.89 - 3.42 (m, 6H),
l,3-dihydro-2H- 2.25 - 1.70 (m, 6H)
pyrrolo[3,4- c]pyridine-2- carboxamide
1541 N-(4-{ [(3S)-l- ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, IH), 8.50 (ESI(+))
(cyclopropylacetyl)p (d, J = 5.0 Hz, IH), 8.29 (s, IH), 7.48 - 7.40 (m, 3H), m/e 407 yrrolidin-3- 6.93 - 6.82 (m, 2H), 5.03 - 4.90 (m, IH), 4.81 - 4.75 (M+H)+ yl] o xy } phenyl) - 1 , 3 - (m, 4H), 3.80 - 3.33 (m, 2H), 2.30 - 1.95 (m, 5H),
dihydro-2H- 1.07 - 0.88 (m, IH), 0.49 - 0.35 (m, 2H), 0.19 - 0.07 pyrrolo[3,4- (m, 2H)
c]pyridine-2- carboxamide
Example 953
N- { 6- [( 1 -acetylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 953 A
tert-butyl 4-(5-nitropyridin-2-yloxy)piperidine- 1 -carboxylate A suspension of pre-washed NaH (0.1 g, 2.48 mmol, 60% percent dispersion in mineral oil) in THF (2 mL) was added to an ice cold solution of 4-hydroxy-piperidine-l- carboxylic acid tert-butyl ester (0.5 g, 2.48 mmol) in dry THF (3mL). The mixture was stirred for 20 minutes, and added to 2-chloro-5-nitro-pyridine (0.36 g, 2.26 mmol) in portions. After the addition was completed, the cooling bath was removed and the reaction mixture was stirred at 22°C overnight. The reaction mixture was cooled in an ice bath and treated with a saturated aqueous sodium bicarbonate solution (5 mL). The reaction mixture was diluted with ethyl acetate (25 mL) and distilled water (25 mL). The separated aqueous phase was extracted with ethyl acetate (3 x 35 mL), and the combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. Chromatography provided the title compound.
Example 953B
tert-butyl 4-(5-aminopyridin-2-yloxy)piperidine- 1 -carboxylate The title compound was prepared as described in Example 274, substituting tert-butyl 4-(5-nitropyridin-2-yloxy)piperidine-l -carboxylate for 5-nitro-N-[4- (propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide.
Example 953C
tert-butyl 4-(5-(isoindoline-2-carboxarnido)pyridin-2-yloxy)piperidine- 1 -carboxylate The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(5-aminopyridin-2-yloxy)piperidine-l -carboxylate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride.
Example 953D
N-(6-(piperidin-4-yloxy)pyridin-3-yl)isoindoline-2-carboxarnide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(5-(isoindoline-2-carboxarnido)pyridin-2-yloxy)piperidine-l -carboxylate for tert-butyl 4- ((4-(5-fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate.
Example 953E
N- { 6- [( 1 -acetylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting N-(6- (piperidin-4-yloxy)pyridin-3-yl)isoindoline-2-carboxarnide for 3-phenylpropan-l-amine and acetic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.37 (s, 1H), 8.26 (d, J = 2.7 Hz, 1H), 7.86 (dd, J = 8.9, 2.7 Hz, 1H), 7.44 - 7.24 (m, 4H), 6.75 (d, J = 8.8 Hz, IH), 5.21 - 5.07 (m, IH), 4.75 (s, 4H), 3.72 - 3.63 (m, IH), 3.40 - 3.11 (m, 2H), 1.97 - 1.85 (m, IH), 1.73 - 1.38 (m, 2H); MS (ESI(+)) m/e 495 (M+H)+. Table 17.
The following Examples were essentially prepared as described in Example 1C, substituting N-(6-(piperidin-4-yloxy)pyridin-3-yl)isoindoline-2-carboxamide for 3- phenylpropan-1 -amine and the appropriate carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid.
Figure imgf000868_0001
Figure imgf000869_0001
Example 966
tert-butyl (2-{4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl}ethyl)carbamate The title compound was prepared as described in Example 272B, substituting tert- butyl 4-aminophenethylcarbamate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, OMSO-d6) δ ppm 8.26 (s, 1H), 7.50 - 7.43 (m, 2H), 7.40 - 7.26 (m, 4H), 7.11 - 7.03 (m, 2H), 6.87 - 6.79 (m, 1H), 4.75 (s, 4H), 3.18 - 3.02 (m, 2H), 2.66 - 2.58 (m, 2H), 1.37 (s, 9H); MS (ESI(+)) m/e 382 (M+H)+.
Example 973
N- { 4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide The title compound was prepared as described in Example 808, substituting
(tetrahydrofuran-3-yl)methanamine for 3-methylbutan-l -amine in Example 808A. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.76 (s, 1H), 7.82 - 7.75 (m, 2H), 7.71 - 7.64 (m, 2H), 7.54 (t, J = 6.1 Hz, 1H), 7.41 - 7.25 (m, 4H), 4.80 (bs, 4H), 3.70 - 3.49 (m, 3H), 2.69 (t, J = 6.7 Hz, 2H), 2.34 - 2.16 (m, 1H), 1.94 - 1.79 (m, 1H), 1.54 - 1.39 (m, 1H); MS (ESI(+)) m/e 402 (M+H)+.
Example 974
N- { 4- [(tetrahydrofuran-3-ylmethyl)sulf amoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 272B, substituting 4- amino-N-((tetrahydrofuran-3-yl)methyl)benzenesulfonamide for 4-amino-N-propylbenzamide and l,3-dihydro-2H-pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.83 (s, 1H), 8.62 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 7.82 - 7.75 (m, 2H), 7.72 - 7.65 (m, 2H), 7.55 (t, J = 6.0 Hz, 1H), 7.44 (d, J = 5.1 Hz, 1H), 4.87 - 4.75 (m, 4H), 3.76 - 3.49 (m, 3H), 2.69 (t, 7 = 6.7 Hz, 2H), 2.34 - 2.16 (m, 1H), 1.94 - 1.79 (m, 1H), 1.54 - 1.39 (m, 1H) ; MS (ESI(+)) m/e 403 (M+H)+.
Example 975
5-cyano-N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 272B, substituting 4- amino-N-((tetrahydrofuran-3-yl)methyl)benzenesulfonamide for 4-amino-N-propylbenzamide and isoindoline-5-carbonitrile for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.83 (s, 1H), 7.89 (s, 1H), 7.83 - 7.74 (m, 3H), 7.72 - 7.64 (m, 2H), 7.59 (d, J = 7.9 Hz, 1H), 7.54 (t, J = 6.1 Hz, 1H), 4.93 - 4.76 (m, 4H), 3.70 - 3.49 (m, 3H), 2.69 (t, J = 6.7 Hz, 2H), 2.31 - 2.05 (m, 1H), 1.94 - 1.78 (m, 1H), 1.54 - 1.39 (m, 1H); MS (ESI(+)) m/e 427 (M+H)+.
Example 979
N- { 4- [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
Example 979A
N-(4-(piperidin-4-yl)phenyl)isoindoline-2-carboxamide tert-Butyl 4-(4-(isoindoline-2-carboxamido)phenyl)-5,6-dihydropyridine-l(2H)- carboxylate (1.00 g, 2.38 mmol) in 20 ml of 1 : 1 methanol/tetrahydrofuran was added to 5% Pd on carbon (wet) (0.200 g) in a 50 ml pressure bottle and stirred for 16 hours at 30 atm and room temperature. The mixture was filtered through a nylon membrane and concentrated. The residue was suspended in dichloromethane, stirred 1 hour and filtered with
dichloromethane washes to provide the title compound. Example 979B
N- { 4- [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4- (piperidin-4-yl)phenyl)isoindoline-2-carboxamide for 3-phenylpropan-l -amine and tetrahydrofuran-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO-<¾) δ ppm 8.26 (s, IH), 7.46 (m, 2H), 7.31 (m, 4H), 7.12 (m, 2H), 4.74 (bs, 4H), 4.53 (m, IH), 4.05 (m, IH), 3.87 (m, IH), 3.70 (m, 3H), 3.36 (m, 2H), 3.12 (m, IH), 2.75 - 2.58 (m, IH), 2.01 (m, 2H), 1.76 (m, 2H), 1.45 (m, 2H); MS (ESI(+)) m/e 420 (M+H). Table 18.
The following Examples were essentially prepared as described in Example 1C, substituting the apropriate amine for 3-phenylpropan-l-amine and the appropriate carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid.
Figure imgf000871_0001
dihydro-2H-isoindole-2- 1H), 2.71 (m, 2H), 1.76 (d, J = 11.8 Hz, 2H), 1.50
carboxamide (m, 2H), 1.32 (s, 6H)
986 N-{4-[l-(morpholin-4- ¾ NMR (400 MHz, DMSO-<¾) δ ppm 8.26 (s, 1H), (ESI(+)) ylacetyl)piperidin-4- 7.46 (m, 2H), 7.33 (m, 4H), 7.10 (m, 2H), 4.74 (bs, m/e 449 yl]phenyl} - 1 ,3-dihydro- 4H), 4.46 (m, 1H), 4.13 (m, 1H), 3.57 (m, 4H), 3.06 (M+H)+ 2H-isoindole-2- (m, 3H), 2.71 - 2.50 (m, 2H), 2.40 (m, 4H), 1.77 (m, carboxamide 2H), 1.56 (m, 1H), 1.40 (m, 1H)
1469 N-(4-{ l-[(2R)- ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.28 (s, 1H), (ESI(+)) tetrahydrofuran-2- 7.47 (m, 2H), 7.32 (m, 4H), 7.13 (m, 2H), 4.75 (s, m/e 420 ylcarbonyl]piperidin-4- 4H), 4.70 (m, 1H), 4.48 (m, 1H), 4.10 (m, 1H), 3.76 (M+H)+ yl jphenyl)- 1,3-dihydro- (m, 2H), 3.08 (m, 1H), 2.69 (m, 2H), 2.03 (m, 2H),
2H-isoindole-2- 1.81 (m, 4H), 1.54 (m, 1H), 1.42 (m, 1H)
carboxamide
1470 N-(4-{ l-[(2S)- ¾ NMR (400 MHz, DMSO-d6) δ ppm 8.28 (s, 1H), (ESI(+)) tetrahydrofuran-2- 7.47 (m, 2H), 7.33 (m, 4H), 7.12 (dd, J = 8.3, 2.5 Hz, m/e 420 ylcarbonyl]piperidin-4- 2H), 4.75 (s, 4H), 4.68 (dd, 7 = 7.5, 5.7 Hz, 1H), 4.49 (M+H)+ yl jphenyl)- 1 ,3-dihydro- (m, 1H), 4.10 (m, 1H), 3.76 (m, 2H), 3.13 (m, 1H),
2H-isoindole-2- 268 (m, 2H), 2.01 (m, 2H), 1.80 (m, 4H), 1.50 (m,
carboxamide 2H)
1471 N-(4-{ l-[(3R)- A- 1361467.0 - ¾ NMR (400 MHz, DMSO-d6) δ (ESI(+)) tetrahydrofuran-3- 8.28 (s, 1H), 7.47 (m, 2H), 7.34 (m, 4H), 7.13 (m, m/e 420 ylcarbonyl]piperidin-4- 2H), 4.75 (s, 4H), 4.54 (m, 1H), 4.08 (m, 1H), 3.88 (M+H)+ yl jphenyl)- 1 ,3-dihydro- (m, 1H), 3.71 (m, 3H), 3.39 (m, 1H), 3.14 (m, 1H),
2H-isoindole-2- 2.66 (m, 2H), 2.01 (m, 2H), 1.79 (m, 2H), 1.46 (m, carboxamide 2H)
Example 1013
N-(4-{ [l-(tetrahydro furan-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide
Example 1013 A
tert-butyl 4-(4-(isoindoline-2-carboxamido)phenoxy)piperidine- 1 -carboxylate
The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(4-aminophenoxy)piperidine-l -carboxylate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride.
Example 1013B
N-(4-(piperidin-4-yloxy)phenyl)isoindoline-2-carboxamide
The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(isoindoline-2-carboxamido)phenoxy)piperidine-l -carboxylate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate.
Example 1013C
N-(4-{ [l-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4- (piperidin-4-yloxy)phenyl)isoindoline-2-carboxamide for 3-phenylpropan-l -amine and tetrahydrofuran-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.20 (s, 1H), 7.47 - 7.27 (m, 6H), 6.93 - 6.86 (m, 2H), 4.74 (s, 4H), 4.58 - 4.47 (m, IH), 3.93 - 3.56 (m, 6H), 3.44 - 3.32 (m, 3H), 2.06 - 1.83 (m, 4H), 1.69 - 1.40 (m, 2H); MS (ESI(+)) m/e 436 (M+H)+.
Table 19.
The following Examples were essentially prepared as described in Example 1C, substituting an appropriate amine for 3-phenylpropan-l -amine and appropriate acid for 4-
(isoindoline-2-carboxamido)benzoic acid.
Figure imgf000873_0001
ylacetyl)piperidin-4- (s, 1H), 7.43 (t, J = 13.2 Hz, 2H), 7.37 - 7.24 (m, 3H), m/e 465 yl] oxy } phenyl)- 1,3- 6.91 (d, J = 9.1 Hz, 2H), 4.74 (s, 4H), 4.71 - 4.45 (m, (M+H)+ dihydro-2H-isoindole-2- 1H), 4.37 (s, 2H), 4.04 - 3.71 (m, 6H), 3.56 (d, J =
carboxamide 15.9 Hz, 2H), 3.47 - 3.20 (m, 4H), 3.13 (s, 2H), 1.97
(s, 2H), 1.62 (dd, J = 33.2, 8.7 Hz, 2H)
N-(4-{ [l- ¾ NMR (300 MHz, DMSO-d6) δ 8.20 (s, 1H), 7.51 - (ESI(+))
(tetrahydrofuran-3- 7.35 (m, 3H), 7.35 - 7.23 (m, 3H), 6.89 (d, J = 9.0 Hz, m/e 450 ylacetyl)piperidin-4- 2H), 4.74 (s, 4H), 4.50 (dd, 7 = 7.7, 3.9 Hz, 1H), 3.92 (M+H)+ yl] oxy } phenyl)- 1,3- - 3.71 (m, 3H), 3.71 - 3.52 (m, 2H), 3.22 (dd, J = 9.8, dihydro-2H-isoindole-2- 4.3 Hz, 3H), 2.45 (s, 3H), 2.13 - 1.80 (m, 3H), 1.67 - carboxamide 1.37 (m, 3H)
Example 1018
N-(4- { 4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
Example 1018 A
N-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide
2,3-Dihydro-lH-pyrrolo[3,4-c]pyridine 2-HCl (1.55 g, 8.03 mmol) was suspended in dimethylformamide (30 ml) and treated with triisopropylethylamine (4.21 ml, 24.08 mmol). After stirring for 20 minutes, the mixture was cooled to -15°C. 2-(4-Isocyanatophenyl)- 4,4,5,5-tetramethyl-l,3,2-dioxaborolane (2.028 g, 8.03 mmol) was dissolved in 10 ml tetrahydrofuran and added via syringe over 10 minutes. The mixture was allowed to warm to room temperature, and it was stirred for 3 hours and concentrated under a stream of nitrogen to minimal volume. The residue was diluted with cold water to give a turbid mixture which was filtered with water washes to provide the title compound after drying.
Example 1018B
tert-butyl 4-(4-(2,3-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)cyclohex-3- enylcarbamate
N-(4-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)-lH-pyrrolo[3,4- c]pyridine-2(3H)-carboxamide (1.692 g, 4.63 mmol), 4-(tert-butoxycarbonylamino)cyclohex- 1 -enyl trifluoromethanesulfonate (1.6 g, 4.63 mmol) and cesium carbonate (3.77 g, 11.58 mmol) were suspended in terahydrofuran (30 ml), methanol (5.00 ml)and water (15.00 ml). Nitrogen was bubbled throught the solution for 10 min when PdCl2(dppf)-dichloro methane adduct (0.189 g, 0.232 mmol) was added and the mixture was heated to 80°C for 7h. After dilution with ethyl acetate and brine, the separated aqueous layer was extracted several times with ethyl acetate and the combined organic layers were dried over magnesium sulfate, filtered and concentrated. Flash chromatography provided the title compound.
Example 1018C
N-(4-(4-aminocyclohex-l-enyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)cyclohex-3- enylcarbamate for tert-butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate.
Example 1018D
N-(4- { 4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for 3- phenylpropan-1 -amine and isobutyric acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.61 (s, 1H), 8.50 (d, 7 = 5.0 Hz, 1H), 8.41 (s, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.56 - 7.48 (m, 2H), 7.43 (d, 7 = 5.1 Hz, 1H), 7.37 - 7.29 (m, 2H), 6.06 - 5.99 (m, 1H), 4.83 - 4.77 (m, 4H), 3.87 - 3.73 (m, 1H), 2.37 (t, J = 6.7 Hz, 2H), 2.11 - 1.97 (m, 1H), 1.95 - 1.82 (m, 1H), 1.80 - 1.50 (m, 1H), 1.38 - 1.20 (m, 2H), 1.00 (dd, 7 = 6.8. 2.5 Hz, 6H); MS (ESI(+)) m/e 405 (M+H)+.
Table 20.
The title compound was prepared as described in Example 1C, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for 3- phenylpropan-1 -amine and the appropriate carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid.
Figure imgf000875_0001
Figure imgf000876_0001
Figure imgf000877_0001
Figure imgf000878_0001
Example 1020
tert-butyl 3 - { [( 1 , 3 -dihydro-2H-isoindol-2 -ylcarbonyl) amino] methyl } azetidine- 1 -carboxylate
The title compound was prepared as described in Example 272B, substituting tert- butyl 3-(aminomethyl)azetidine-l -carboxylate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- de) δ ppm 7.37 - 7.23 (m, 4H), 6.58 - 6.48 (m, 1H), 4.58 (s, 4H), 3.91 - 3.75 (m, 2H), 3.65 - 3.51 (m, 2H), 3.30 - 3.20 (m, 2H), 2.68 - 2.55 (m, 1H), 1.35 (s, 9H); MS (ESI(+)) m/e 332 (M+H)+.
Example 1021
tert-butyl [( 1 -{ 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } azetidin-3- yl)methyl] c arb amate Example 1021 A
tert-butyl (1 -(4-nitrophenyl)azetidin-3-yl)methylcarbamate A solution of l-fluoro-4-nitrobenzene (0.61 g, 4.32 mmol) and tert-butyl azetidin-3- ylmethylcarbamate (0.886 g, 4.76 mmol) in dimethylformamide (8.65 ml) was treated with potassium carbonate (0.896 g, 6.48 mmol) and the suspension was heated at 55°C (12 pm) for 3 hours and at ambient temperature for 16 hours. The reaction was poured into water and the suspension was filtered. The solid was washed with water and dried to provide the title compound.
Example 102 IB
tert-butyl (l-(4-aminophenyl)azetidin-3-yl)methylcarbamate
The title compound was prepared as described in Example 272A, substituting tert- butyl (l-(4-nitrophenyl)azetidin-3-yl)methylcarbamate for 4-nitro-N-propylbenzamide.
Example 1021C
tert-butyl [( 1 -{ 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } azetidin-3- yl)methyl]carbamate
The title compound was prepared as described in Example 272B, substituting tert- butyl (l-(4-aminophenyl)azetidin-3-yl)methylcarbamate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- de) δ ppm 8.03 (s, 1H), 7.39 - 7.25 (m, 6H), 7.07 - 6.94 (m, 1H), 6.33 (d, 7 = 8.8 Hz, 2H), 4.72 (s, 4H), 3.75 (t, 7 = 7.4 Hz, 2H), 3.48 - 3.40 (m, 2H), 3.22 - 3.14 (m, 2H), 2.76 - 2.65 (m, 1H), 1.38 (s, 9H); MS (ESI(+)) m/e 423 (M+H)+.
Example 1046
N-[4-({ [4-(acetylamino)phenyl] sulfonyl } amino)phenyl] -1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- arninophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline-2-carboxamide and 4-(acetylamino)phenyl] sulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.72 (s, 1 H) 8.62 (d, 7=4.88 Hz, 1 H) 7.73 (d, 7=5.49 Hz, 1 H) 7.61 - 7.69 (m, 4 H) 7.36 (d, 7=8.54 Hz, 2 H) 6.98 (d, 7=8.85 Hz, 2 H) 4.88 (d, 7=7.02 Hz, 4 H) 2.00 - 2.10 (m, 3 H); MS (APCI(+)) m/e 452 (M+H)+.
Example 1047
N- { 4- [(propylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 883, substituting N-(4- aminophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline-2-carboxamide and propylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.72 (s, 1 H) 8.62 (d, 7=5.49 Hz, 1 H) 7.73 (d, 7=5.49 Hz, 1 H) 7.46 (d, 7=8.54 Hz, 2 H) 7.14 (d, 7=8.85 Hz, 2 H) 4.91 (d, 7=6.10 Hz, 4 H) 2.98 - 3.06 (m, 2 H) 1.66 - 1.78 (m, 2 H) 0.96 (t, 7=7.48 Hz, 3 H); MS (APCI(+)) m/e 361 (M+H)+.
Example 1048
N-(4-{ [(4-propylphenyl)sulfonyl]amino}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- arninophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- arninophenyl)isoindoline-2-carboxarnide and (4-propylphenyl)sulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (300 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.59 (s, 1H), 8.49 (d, 7 = 5.0 Hz, 1H), 8.33 (s, 1H), 7.64 - 7.58 (m, 2H), 7.45 - 7.33 (m, 4H), 7.33 (s, 1H), 6.99 - 6.92 (m, 2H), 4.79 - 4.72 (m, 4H), 2.57 (dd, 7 = 17.1, 9.3 Hz, 1H), 1.65 - 1.49 (m, 2H), 0.86 (t, 7 = 7.3 Hz, 3H); MS (ESI(+)) m/e 437 (M+H)+.
Example 1049
N- { 4-[(butylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- aminophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline-2-carboxamide and butylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.71 (s, 1 H) 8.61 (d, 7=5.19 Hz, 1 H) 7.70 (d, 7=5.49 Hz, 1 H) 7.47 (d, 7=8.85 Hz, 2 H) 7.14 (d, 7=8.85 Hz, 2 H) 4.90 (d, 7=3.66 Hz, 4 H) 2.97 - 3.08 (m, 2 H) 1.61 - 1.72 (m, 2 H) 1.30 - 1.44 (m, 2 H) 0.85 (t, 7=7.32 Hz, 3 H); MS (APCI(+)) m/e 375 (M+H)+.
Example 1050
N-{4-[({ [(lS,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-l- yl]methyl } sulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 883, substituting N-(4- aminophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline-2-carboxamide and (lS,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept- l-yl]methyl}sulfonyl chloride for (3-methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.72 (s, 1 H) 8.61 (d, 7=5.19 Hz, 1 H) 7.71 (d, 7=5.49 Hz, 1 H) 7.49 (d, 7=8.85 Hz, 2 H) 7.18 (d, 7=8.85 Hz, 2 H) 4.90 (d, 7=3.97 Hz, 4 H) 2.81 (s, 2 H) 2.27 - 2.41 (m, 2 H) 2.07 (t, 7=4.43 Hz, 1 H) 1.94 - 2.03 (m, 2 H) 1.34 - 1.66 (m, 2 H) 1.02 (s, 3 H) 0.79 (s, 3 H); MS (APCI(+)) m/e 469 (M+H)+.
Example 1051
N- { 4- [(ethylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 883, substituting N-(4- aminophenyl)-lH^yrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline-2-carboxamide and ethylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.70 - 8.75 (m, 1 H) 8.60 - 8.64 (m, 7=5.65, 5.65 Hz, 1 H) 7.74 (d, 7=5.19 Hz, 1 H) 7.46 (d, 7=8.85 Hz, 2 H) 7.15 (d, 7=8.54 Hz, 2 H) 4.91 (d, 7=7.02 Hz, 4 H) 3.04 (q, 7=7.32 Hz, 2 H) 1.23 (t, 7=7.32 Hz, 3 H); MS (APCI(+)) m/e 347 (M+H)+.
Example 1052
N-{4-[(benzylsulfonyl)amino]phenyl}-l,3-dmydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 883, substituting N-(4- arninophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline-2-carboxamide and benzylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.72 (s, 1 H) 8.61 (d, 7=4.88 Hz, 1 H) 7.70 (d, 7=5.19 Hz, 1 H) 7.46 (d, 7=8.85 Hz, 2 H) 7.28 - 7.37 (m, 5 H) 7.11 (d, 7=8.85 Hz, 2 H) 4.90 (d, 7=3.05 Hz, 4 H) 4.37 (s, 2 H); MS (APCI(+)) m/e 409 (M+H)+.
Example 1053
N-(4- { [(4-fluorophenyl)sulfonyi] amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- arninophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline-2-carboxamide and (4-fluorophenyl)sulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.71 (s, 1 H) 8.61 (d, 7=5.19 Hz, 1 H) 7.78 (dd, 7=8.85, 5.19 Hz, 2 H) 7.67 - 7.73 (m, 1 H) 7.28 - 7.43 (m, 4 H) 6.98 (d, 7=8.85 Hz, 2 H) 4.87 (d, 7=4.27 Hz, 4 H); MS (APCI(+)) m/e 412 (M+H)+.
Example 1054
N-{4-[(thiophen-2-ylsulfonyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- arninophenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline-2-carboxamide and thiophen-2-ylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.70 (s, 1 H) 8.61 (d, 7=4.88 Hz, 1 H) 7.81 (d, 7=4.88 Hz, 1 H) 7.69 (d, 7=5.19 Hz, 1 H) 7.49 (d, 7=2.75 Hz, 1 H) 7.42 (d, 7=8.85 Hz, 2 H) 7.09 - 7.13 (m, 1 H) 7.04 (d, 7=8.85 Hz, 2 H) 4.88 (d, 7=3.36 Hz, 4 H); MS (APCI(+)) m/e 401 (M+H)+. Example 1088
N- [4-(piperidin- 1 -ylsulfonyl)phenyl] - 1
The title compound was prepared as described in Example 272B, substituting 4- (piperidin-l-ylsulfonyl)aniline for 4-amino-N-propylbenzamide and l,3-dihydro-2H- pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO-d6) δ ppm 8.89 (s, 1H), 8.62 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 7.86 - 7.79 (m, 2H), 7.66 - 7.59 (m, 2H), 7.44 (d, J = 5.0 Hz, 1H), 4.89 - 4.76 (m, 4H), 3.25 - 3.00 (m, 1H), 2.95 - 2.82 (m, 4H), 1.57 - 1.44 (m, 4H), 1.41 - 1.31 (m, 1H); MS (ESI(+)) m/e 387 (M+H)+.
Example 1246
methyl l-{4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-ylcarbonyl)amino]phenyl}azetidine-3- carboxylate
Example 1246 A
methyl 1 -(4-nitrophenyl)azetidine-3-carboxylate A solution of methyl azetidine-3-carboxylate hydrochloride (1.236 g, 8.15 mmol) and N-methylmorpholine (2.338 ml, 21.26 mmol) in dimethylformamide (10 mL) was treated with a solution of 1 -fluoro-4-nitrobenzene (1 g, 7.09 mmol) in dimethylformamide (7 mL) and the reaction was allowed to stir at room temperature for 60 hours. Water (50 mL) was added and the resulting suspension was stirred 10 minutes and filtered. The collected solid was washed with water and dried under vacuum. Hash chromatography of the collected solid provided the title compound.
Example 1246B
methyl 1 -(4-aminophenyl)azetidine-3-carboxylate The title compound was prepared as described in Example 272A, substituting methyl 1 -(4-nitrophenyl)azetidine-3-carboxylate for 4-nitro-N-propylbenzamide.
Example 1246C
methyl l-{4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-ylcarbonyl)amino]phenyl}azetidine-3- carboxylate
The title compound was prepared as described in Example 272B, substituting methyl l-(4-aminophenyl)azetidine-3-carboxylate for 4-amino-N-propylbenzamide and 1,3-dihydro- 2H-pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.60 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.15 (s, 1H), 7.42 (d, 7 = 5.1 Hz, 1H), 7.36 - 7.29 (m, 2H), 6.44 - 6.37 (m, 2H), 4.80 - 4.72 (m, 4H), 4.02 - 3.93 (m, 2H), 3.86 - 3.77 (m, 2H), 3.68 (s, 3H), 3.66 - 3.56 (m, 1H); MS (ESI(+)) m/e 353 (M+H)+.
Example 1247
N-(4-{3-[(3-methylbutyl)carbamoyl]azetidin-l-yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide Example 1247 A
l-(4-(23-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)azetidine-3-carboxylic acid
The title compound was prepared as described in Example IB, substituting methyl 1- { 4-[( 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-ylcarbonyl)amino]phenyl } azetidine-3- carboxylate for methyl 4-(isoindoline-2-carboxamido)benzoate.
Example 1247B
N-(4- { 3-[(3-methylbutyl)carbamoyl] azetidin- 1 -yljphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example IC, substituting 3- methylbutan-1 -amine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)phenyl)azetidine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-<¾) δ ppm 8.59 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.13 (s, 1H), 7.90 (t, 7 = 5.5 Hz, 1H), 7.42 (d, 7 = 4.8 Hz, 1H), 7.34 - 7.27 (m, 2H), 6.41 - 6.34 (m, 2H), 4.79 - 4.73 (m, 4H), 3.94 - 3.85 (m, 2H), 3.76 - 3.69 (m, 2H), 3.47 - 3.36 (m, 1H), 3.13 - 3.04 (m, 2H), 1.65 - 1.48 (m, 1H), 1.35 - 1.24 (m, 2H), 0.87 (d, 7 = 6.6 Hz, 6H); MS (ESI(+)) m/e 408 (M+H)+.
Example 1248
N-(4- { 3-[(tetrahydrofuran-2-ylmethyl)carbamoyl] azetidin- 1 -yljphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example IC, substituting
(tetrahydrofuran-2-yl)methanamine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)azetidine-3-carboxylic acid for 4-(isoindoline- 2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.59 (s, 1H), 8.49 (d, 7 = 5.0 Hz, 1H), 8.13 (s, 1H), 8.05 (t, 7 = 5.8 Hz, 1H), 7.42 (d, 7 = 5.1 Hz, 1H), 7.35 - 7.27 (m, 2H), 6.41 - 6.34 (m, 2H), 4.79 - 4.73 (m, 4H), 3.94 - 3.68 (m, 6H), 3.68 - 3.55 (m, 1H), 3.54 - 3.39 (m, 1H), 3.20 - 3.07 (m, 2H), 1.93 - 1.71 (m, 3H), 1.55 - 1.41 (m, 1H); MS (ESI(+)) m/e 422 (M+H)+.
Example 1249
N-(4- { 3-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example IC, substituting
(tetrahydro-2H-pyran-4-yl)methanamine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro- lH-pyrrolo[3,4-c]pyridine-2-carboxarnido)phenyl)azetidine-3-carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.59 (s,
1H), 8.49 (d, 7 = 5.0 Hz, 1H), 8.13 (s, 1H), 7.97 (t, 7 = 5.8 Hz, 1H), 7.42 (d, 7 = 5.1 Hz, 1H), 7.34 - 7.27 (m, 2H), 6.41 - 6.34 (m, 2H), 4.79 - 4.73 (m, 4H), 3.95 - 3.86 (m, 2H), 3.86 - 3.78 (m, 2H), 3.77 - 3.69 (m, 2H), 3.51 - 3.40 (m, 1H), 3.31 - 3.19 (m, 2H), 3.02 - 2.94 (m, 2H), 1.69 - 1.48 (m, 3H), 1.22 - 1.04 (m, 2H); MS (ESI(+)) m/e 436 (M+H)+.
Example 1250
N-{ 4-[3-(benzylcarbamoyl)azetidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example IC, substituting benzylamine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2- carboxamido)phenyl)azetidine-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.59 (s, 1H), 8.53 - 8.45 (m, 2H), 8.13 (s, 1H), 7.42 (d, J = 5.0 Hz, 1H), 7.37 - 7.22 (m, 7H), 6.43 - 6.35 (m, 2H), 4.76 (m, 4H), 4.30 (d, J = 5.9 Hz, 2H), 3.99 - 3.88 (m, 2H), 3.83 - 3.72 (m, 2H), 3.57 - 3.46 (m, 1H); MS (ESI(+)) m/e 428 (M+H)+.
Example 1251
N-{4-[3-(cyclopentylcarbamoyl)azetidin-l-yl]phenyl} -l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example IC, substituting cyclopentylamine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)phenyl)azetidine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.59 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.13 (s, 1H), 7.91 (d, J = 12 Hz, 1H), 7.42 (d, 7 = 5.1 Hz, 1H), 7.34 - 7.27 (m, 2H), 6.41 - 6.33 (m, 2H), 4.79 - 4.73 (m, 4H), 4.06 - 3.94 (m, 1H), 3.92 - 3.84 (m, 2H), 3.76 - 3.66 (m, 2H), 3.46 - 3.33 (m, 1H), 1.86 - 1.72 (m, 2H), 1.67 - 1.30 (m, 6H); MS (ESI(+)) m/e 406 (M+H)+.
Example 1252
N-(4- { 3-[(cyclopentylmethyl)carbamoyl]azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example IC, substituting cyclopentylmethamine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)phenyl)azetidine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.59 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.13 (s, 1H), 7.96 (t, 7 = 5.7 Hz, 1H), 7.42 (d, 7 = 4.7 Hz, 1H), 7.34 - 7.27 (m, 2H), 6.41 - 6.33 (m, 2H), 4.81 - 4.72 (m, 4H), 3.94 - 3.85 (m, 2H), 3.77 - 3.68 (m, 2H), 3.50 - 3.37 (m, 1H), 3.04 - 2.97 (m, 2H), 2.04 - 1.89 (m, 1H), 1.71 - 1.39 (m, 6H), 1.25 - 1.08 (m, 2H); MS (ESI(+)) m/e 420 (M+H)+.
Example 1253
N-(4-{ 3-[(2-methoxyethyl)carbamoyl]azetidin-l-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide The title compound was prepared as described in Example 1C, substituting 2- methoxyeth-l-ylamine for 3-phenylpropan-l-amine and l-(4-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)phenyl)azetidine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.59 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.13 (s, 1H), 8.05 (t, 7 = 5.5 Hz, 1H), 7.42 (d, 7 = 5.1 Hz, 1H), 7.35 - 7.27 (m, 2H), 6.42 - 6.34 (m, 2H), 4.79 - 4.73 (m, 4H), 3.93 - 3.86 (m, 2H), 3.73 (t, 7 = 6.6 Hz, 2H), 3.52 - 3.41 (m, 1H), 3.38 - 3.30 (m, 2H), 3.27 - 3.21 (m, 5H); MS (ESI(+)) m/e 396 (M+H)+.
Example 1268
N-(6-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}pyridazin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting (S)- (tetrahydrofuran-2-yl)methamine for 3-phenylpropan-l-amine and 6-(isoindoline-2- carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.85 (t, 7 = 6.1 Hz, 1H), 8.32 (d, 7 = 9.3 Hz, 1H), 8.12 (d, 7 = 9.3 Hz, 1H), 7.41 - 7.28 (m, 4H), 5.04 - 4.72 (m, 4H), 4.04 (p, 7 = 6.2 Hz, 1H), 3.85 - 3.74 (m, 1H), 3.69 - 3.58 (m, 1H), 3.38 (dd, 7 = 11.2, 5.0 Hz, 2H), 2.01 - 1.74 (m, 3H), 1.71 - 1.54 (m, 1H); MS (ESI(+)) m/e 368 (M+H)+.
Example 1285
N- { 4-[(4-fluorobenzyl)(3-methylbutanoyl)amino]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
Example 1285A
tert-butyl 4-(4-fluorobenzylamino)butylcarbamate Teri-butyl 4-bromobutylcarbamate (0.735 g, 2.91 mmoles), (4- fluorophenyl)methanamine (0.333 g, 2.91 mmoles) and potassium carbonate (0.806 g, 5.83 mmoles) were stirred in acetonitrile (15 mL) at 100°C for 1 hour. The reaction mixture was cooled, the solvent waqs concentrated and the residue was taken into dichloromethane and washed with water twice. The organic layers were combined, dried over magnesium sulfate, filtered and concentrated to provide the title compound which was used without further purification in the next step.
Example 1285B
tert-butyl 4-(N-(4-fluorobenzyl)-3-methylbutanamido)butylcarbamate The title compound was prepared as described in Example 278, substituting 3- methylbutanoyl chloride for acetyl chloride and tert-butyl 4-(4- fluorobenzylamino)butylcarbamate for 5-amino-N-(4-(propylcarbamoyl)phenyl)isoindoline- 2-carboxamide.
Example 1285C
N-(4-aminobutyl)-N-(4-fluorobenzyl)-3-methylbutan amide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(N-(4-fluorobenzyl)-3-methylbutanamido)butylcarbamate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate.
Example 1285D
N- { 4-[(4-fluorobenzyl)(3-methylbutanoyl)amino]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 272B, substituting N-(4- aminobutyl)-N-(4-fluorobenzyl)-3-methylbutanamide for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (400 MHz, CDC13) δ ppm 7.34 - 7.27 (m, 4H), 7.23 (dd, J = 8.5, 5.5 Hz, 1H), 7.13 (dd, J = 8.5, 5.5 Hz, 1H), 7.06 (t, J = 8.6 Hz, 1H), 6.99 (t, J = 8.6 Hz, 1H), 5.49 - 5.17 (m, 1H), 4.72 (m, 4H), 4.56 (d, J = 17.7 Hz, 2H), 3.34 (m, 4H), 2.29 (m, 2H), 2.23 - 2.12 (m, 1H), 1.68 - 1.50 (m, 4H), 1.01 - 0.93 (d, J = 6.9 Hz, 6H); MS (APCI(+)) m/e 426 (M+H) +.
Example 1286
N-[4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6H-furo[2',3':2,3]cyclobuta[l,2-c]quinolin-6- yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide
Example 1286 A
4-(but-3-enyloxy)-6-chloroquinolin-2(lH)-one To a solution of 6-chloro-4-hydroxyquinolin-2(lH)-one (800 mg, 4.09 mmol) and N,N-diisopropylethylamine (1415 μΐ, 8.18 mmol) in dimethylformamide (13.6 ml) was added 4-bromo-l-butene (415 μΐ, 4.09 mmol). The solution was heated to 60 °C and stirred for 18 hours. The reaction mixture was purified by column chromatography to provide the title compound.
Example 1286B
9-chloro-3,3a,4,4a-tetrahydro-2/f-furo[2',3':2,3]cyclobuta[l,2-c]quinolin-5(6/f)-one
A solution of 4-(but-3-enyloxy)-6-chloroquinolin-2(lH)-one (600 mg, 2.403 mmol) in benzene (240 mL) was placed under a 450 W Hg UV lamp (fitted with a condenser for cooling) and stirred for 4 days (96 hours). The mixture was then cooled, concentrated in vacuo, and taken up in -75 mL of methylene chloride (with mild heating to dissolve as much as possible). The sample, which was a mixture of regioisomers, was purified by column chromatography. Concentration of the compound that eleuted second provided the title compound.
Example 1286C
ieri-butyl [4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6/f-furo[2',3':2,3]cyclobuta[l,2- c]quinolin-6-yl)butyl]carbamate
To a solution of 9-chloro-3,3a,4,4a-tetrahydro-2/f-furo[2',3':2,3]cyclobuta[l,2- c]quinolin-5(6/f)-one (200 mg, 0.801 mmol) in dimethylformamide (4 ml) at 0°C was slowly added sodium hydride (19 mg, 0.801 mmol) over 15 minutes. The suspension was allowed to warm to room temperature. The mixture stirred for 45 minutes and 4-(Boc-amino)butyl bromide (202 mg, 0.801 mmol) was added. The solution was stirred for 15 hours, followed by addition of 0.25 mL methanol. Column chromatography provided the title compound.
Example 1286D
6-(4-aminobutyl)-9-chloro-3,3a,4,4a-tetrahydro-2/f-furo[2',3':2,3]cyclobuta[l,2-c]quinolin-
5(6//)-one
The title compound was prepared as described in Example 2D, substituting feri-butyl [4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6/f-furo[2',3':2,3]cyclobuta[l,2-c]quinolin-6- yl)butyl] carbamate for tert-butyl 4-((4-(5-fluoroisoindoline-2- carboxamido)benzamido)methyl)benzylcarbamate.
Example 1286E
N-[4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6H-furo[2',3':2,3]cyclobuta[l,2-c]quinolin-6- yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide The title compound was prepared as described in Example 272B, substituting 6-(4- aminobutyl)-9-chloro-3,3a,4,4a-tetrahydro-2/f-furo[2',3':2,3]cyclobuta[l,2-c]quinolin-5(6//)- one for 4-amino-N-propylbenzamide and l,3-dihydro-2H-pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (400 MHz, CDC13) δ ppm 8.58 (s, IH), 8.54 (d, J = 4.9 Hz, 1 H), 7.29 (d, J = 4.9 Hz, 1 H), 7.25 (m, 1 H), 7.23 (d, J = 2.6 Hz, 1 H), 6.92 (d, J = 8.9 Hz, 1 H), 4.84 (t, J = 5.6 Hz, 1 H), 4.74 (bs, 4H), 4.46 (t, J = 8.1 Hz, 1 H),
4.22 (m, IH), 4.05 (m, IH), 3.91 (m, IH), 3.39 (m , 3H), 2.93 (m, IH), 2.31 (m ,1H), 2.22 (m, IH), 1.84 (m, IH), 1.69 (m, 5H); MS (ESI(+)) m/e 467 (M+H)+.
Example 1287
N- { 4-[7-chloro- 1 -(2-hydroxyethyl)-3-oxo- 1 ,3-dihydrocyclobuta[c]quinolin-4(2H)-yl]butyl} - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide To a solution of N-[4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6H- furo[2',3':2,3]cyclobuta[l,2-c]quinolin-6-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide (30 mg, 0.064 mmol) in dimethylformamide (292 uL) and water (292 uL) was added sodium hydroxide (1.679 μΐ, 0.064 mmol). The solution was stirred for 18 hours and then brought to pH ~7 by dropwise addition of 1M HCl. Column chromatography of the wet, crude mixture provided the title compound. ¾ NMR (400 MHz, CDC13) δ ppm 8.58 (s, IH), 8.54 (d, 7 = 5.1 Hz, 1 H), 7.54 (d, 7 = 2.4 Hz, 1 H), 7.46 (dd, 7 = 9.1, 2.4 Hz, 1 H), 7.37 (d, 7 = 9.1 Hz, 1 H), 7.25 (m, IH), 5.06 (t, 7 = 5.7 Hz, 1 H) 4.77 (bs, 2H), 4.75 (bs, 2H), 4.33 (t, 7 = 7.4 Hz, 2 H), 3.87 (m, 2H), 3.74 (m, 2H), 3.46 (m, 2H), 3.37 (dd, 7 = 14.0, 4.5 Hz, 1 H), 2.86 (dd, 7 = 14.0, 1.3 Hz, 1 H), 2.27 (m, IH), 1.97 (m, IH), 1.82 (m, 2H), 1.71 (m, 2H); MS (ESI(+)) m/e 467 (M+H)+. Example 1290
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}pyridazin-3-yl)-1 -dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting (R)- (tetrahydrofuran-2-yl)methamine for 3 -phenylpropan- 1 -amine and 6-(isoindoline-2- carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.85 (t, 7 = 6.1 Hz, 1H), 8.32 (d, 7 = 9.3 Hz, 1H), 8.12 (d, J = 9.3 Hz, 1H), 7.41 - 7.28 (m, 4H), 5.00 - 4.71 (m, 4H), 4.04 (p, J = 6.2 Hz, 1H), 3.85 - 3.74 (m, 1H), 3.70 - 3.58 (m, 1H), 3.44 - 3.33 (m, 3H), 1.99 - 1.71 (m, 2H), 1.69 - 1.54 (m, 1H); MS (ESI(+)) m/e 368 (M+H)+.
Table 21.
The following Examples were essentially prepared as described in Example 1C, substituting N-(4-aminophenyl)- lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 3- phenylpropan-1 -amine and the appropriate carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid.
Figure imgf000888_0001
carboxamide
1370 N-{4-[(bicyclo[2.2.1]hept- ¾ NMR (400 MHz, DMSO/D20, 90°C) δ 8.66 (APCI (+)) 2-ylacetyl)amino]phenyl } - (s, 1H), 8.56 (d, 7 = 5.3 Hz, 1H), 7.60 (d, 7 = 5.2 m/e 391 l,3-dihydro-2H- Hz, 1H), 7.43 (m, 4H), 4.86 (s, 4H), 2.25 (dd, 7 = (M+H)+ pyrrolo[3,4-c]pyridine-2- 14.1, 7.8 Hz, 1H), 2.20 (s, 1H), 2.12 (dd, 7 =
carboxamide 14.0, 7.6 Hz, 1H), 1.98 (d, 7 = 17.2 Hz, 1H), 1.90
(s, 1H), 1.41 (m, 4H), 1.14 (m, 4H)
1371 N-{4-[(l,3-thiazol-5- ¾ NMR (400 MHz, DMSO/D20, 90°C) δ 9.20 (APCI (+)) ylcarbonyl)amino]phenyl } - (s, 1H), 8.67 (s, 1H), 8.60 (s, 1H), 8.57 (d, 7 = 5.3 m/e 366 l,3-dihydro-2H- Hz, 1H), 7.61 (d, 7 = 5.3 Hz, 4H), 7.55 (m, 4H) (M+H)+ pyrrolo[3,4-c]pyridine-2- carboxamide
1372 N-(4-{ [(4-oxo-4,5,6,7- ¾ NMR (400 MHz, DMSO/D20, 90°C) δ 8.65 (APCI (+)) tetrahydro- 1 -benzofuran-3- (s, 1H), 8.55 (d, 7 = 5.2 Hz, 1H), 8.26 (d, 7 = 14.4 m/e 417 yl)carbonyl] amino jphenyl) Hz, 1H), 7.55 (m, 5H), 4.86 (s, 4H), 2.96 (m, (M+H)+ -l,3-dihydro-2H- 2H), 2.64 (m, 2H), 2.18 (m, 2H)
pyrrolo[3,4-c]pyridine-2- carboxamide
Example 1369
N-{ 7-oxo-7-[(3-phenylpropyl)amino]heptyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting 7- (isoindoline-2-carboxamido)heptanoic acid for 4-(isoindoline-2-carboxamido)benzoic
acid. Example 1373
N-(4- { 2-[(3-methylbutanoyl)amino]ethyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide
Example 1373 A
N-(4-(2-aminoethyl)phenyl)isoindoline-2-carboxamide
The title compound was prepared as described in Example 2D, substituting tert-butyl (2-{4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl}ethyl)carbamate for tert-butyl 4- ((4-(5-fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate.
Example 1373B
N-(4- { 2-[(3-methylbutanoyl)amino]ethyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 1C, substituting N-(4-(2- aminoethyl)phenyl)isoindoline-2-carboxamide for 3-phenylpropan-l-amine and 3- methylbutanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO- , Temp=90°C) δ 7.50 - 7.40 (m, 2H), 7.40 - 7.24 (m, 4H), 7.13 - 7.02 (m, 2H), 4.76 (s, 4H), 2.68 (t, 7 = 7.3 Hz, 2H), 2.07 - 1.84 (m, 3H), 0.95 - 0.76 (m, 6H). MS (ESI (+)) m/e 366 (M+H)+.
Table 22.
The following Examples were essentially prepared as described in Example 1C, substituting N-(4-(2-aminoethyl)phenyl)isoindoline-2-carboxamide for 3-phenylpropan-l- amine and the appropriate carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid.
Figure imgf000889_0001
Figure imgf000890_0001
Example 1404
N-(4-{ [l-(2-cyclopropylethyl)piperidin-4-yl]oxy}phenyl)-1 -dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The tide compound was prepared as described in Example 429, substituting 2- cyclopropylacetaldehyde for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH- pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.54 - 8.58 (m, 2 H) 8.08 (s, IH) 7.72 - 7.77 (m, 2 H) 7.10 (d, 7=4.88 Hz, 1 H) 7.01 (d, 7=9.16 Hz, 2 H) 4.82 - 4.88 (m, 4 H) 3.71 (s, 1 H) 2.74 - 2.82 (m, 2 H) 2.43 - 2.50 (m, 2 H) 2.22 - 2.31 (m, 2 H) 1.97 (s, 2 H) 1.79 - 1.90 (m, 2 H) 1.35 - 1.47 (m, 2 H) 0.70 (s, 1 H) 0.36 - 0.45 (m, 2 H) 0.05 (q, 7=4.78 Hz, 2 H); MS (APCI(+)) m/e 407 (M+H)+.
Example 1405
N-(4-{ [l-(2-cyclopentylethyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 429, substituting 2- cyclopentylacetaldehyde for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH- pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.54 - 8.58 (m, 2 H) 8.08 (s, IH) 7.72 - 7.78 (m, 2 H) 7.10 (d, 7=4.88 Hz, 1 H) 7.00 - 7.04 (m, 2 H) 4.82 - 4.90 (m, 4 H) 4.21 - 4.31 (m, 1 H) 2.73 - 2.83 (m, 2 H) 2.34 - 2.40 (m, 2 H) 2.20 - 2.29 (m, 2 H) 1.96 - 2.03 (m, 2 H) 1.67 - 1.93 (m, 5 H) 1.40 - 1.62 (m, 6 H) 1.04 - 1.17 (m, 2 H); MS (APCI(+)) m/e 435 (M+H)+.
Example 1406
N-(4-{ [l-(2-methylbutyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide
The title compound was prepared as described in Example 429, substituting 2- methylbutanal for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4- c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.52 - 8.58 (m, 2 H) 8.08 (s, IH) 7.74 (d, 7=8.85 Hz, 2 H) 7.10 (d, 7=4.58 Hz, 1 H) 6.97 - 7.05 (m, 2 H) 4.84 (d, 7=6.71 Hz, 4 H) 2.72 (d, 7=10.68 Hz, 2 H) 2.13 - 2.26 (m, 3 H) 2.01 - 2.07 (m, 2 H) 1.91 - 2.00 (m, 2 H) 1.83 (s, 2 H) 1.54 (s, 2 H) 1.14 (s, 1 H) 0.81 - 0.95 (m, 6 H); MS (APCI(+)) m/e 409 (M+H)+.
Example 1407
N-(4-{ [l-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide The title compound was prepared as described in Example 429, substituting tetrahydrofuran-3-carbaldehyde for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)- lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, Pyridine-i/5. Temp=90°C) δ ppm 8.53 - 8.58 (m, 1 H) 8.08 (s, 1 H) 7.70 - 7.77 (m, 2 H) 7.10 (d, 7=5.19 Hz, 1 H) 7.01 (d,
7=8.85 Hz, 2 H) 4.84 (d, 7=7.63 Hz, 4 H) 4.19 - 4.27 (m, 1 H) 3.75 - 3.90 (m, 2 H) 3.67 - 3.72 (m, 1 H) 3.56 (dd, 7=8.55, 5.80 Hz, 1 H) 2.65 - 2.82 (m, 2 H) 2.31 - 2.45 (m, 1 H) 2.15 - 2.31 (m, 4 H) 1.71 - 2.00 (m, 5 H) 1.48 - 1.59 (m, 1 H); MS (APCI(+)) m/e 423 (M+H)+.
Example 1408
N-(4-{ [l-(3,3-dimethylbutyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 429, substituting 3,3- dimethylbutanal for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4- c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.52 - 8.58 (m, 2 H) 8.09 (s, 1 H) 7.71 - 7.78 (m, 2 H) 7.10 (d, 7=4.88 Hz, 1 H) 6.99 - 7.04 (m, 2 H) 4.84 (dd, 7=8.39, 1.68 Hz, 4 H) 3.85 (d, 7=13.43 Hz, 1 H) 2.75 - 2.85 (m, 2 H) 2.38 - 2.47 (m, 2 H) 2.21 - 2.34 (m, 2 H) 1.98 (d, 7=2.14 Hz, 2 H) 1.78 - 1.91 (m, 2 H) 1.39 - 1.49 (m, 2 H) 0.84 - 0.92 (m, 9 H); MS (APCI(+)) m/e 423 (M+H)+.
Example 1409
N-(4-{ [l-(cyclohexylmethyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 429, substituting cyclohexanecarbaldehyde for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH- pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.53 - 8.57 (m, 2 H) 8.08 (s, 1 H) 7.69 - 7.77 (m, 2 H) 7.10 (s, 1 H) 6.97 - 7.04 (m, 2 H) 4.82 - 4.87 (m, 4 H) 4.20 - 4.27 (m, 1 H) 2.73 (t, 7=10.68 Hz, 2 H) 2.17 - 2.26 (m, 2 H) 2.13 (d, 7=7.02 Hz, 2 H) 1.93 - 2.01 (m, 2 H) 1.76 - 1.87 (m, 4 H) 1.55 - 1.72 (m, 3 H) 1.44 - 1.54 (m, 1 H) 1.09 - 1.29 (m, 3 H) 0.89 (d, 7=12.51 Hz, 2 H); MS (APCI(+)) m/e 435 (M+H)+.
Example 1410
N-(4-{ [l-(3-methylbutyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2 -carboxamide
The title compound was prepared as described in Example 429, substituting 3- methylbutanal for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4- c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.53 - 8.57 (m, 2 H) 8.09 (s, 1 H) 7.70 - 7.78 (m, 2 H) 7.10 (d, 7=5.19 Hz, 1 H) 6.98 - 7.04 (m, 2 H) 4.79 - 4.89 (m, 4 H) 4.26 (d, 7=3.66 Hz, 1 H) 2.72 - 2.83 (m, 2 H) 2.34 - 2.41 (m, 2 H) 2.21 - 2.30 (m, 2 H) 1.96 - 2.03 (m, 2 H) 1.79 - 1.91 (m, 2 H) 1.54 - 1.68 (m, 1 H) 1.35 - 1.44 (m, 2 H) 0.86 - 0.90 (m, 6 H); MS (APCI(+)) m/e 408 (M+H)+.
Example 1411
N-(4- { [1 -(cyclopentylmethyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The tide compound was prepared as described in Example 429, substituting cyclopentanecarbaldehyde for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH- pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.53 - 8.57 (m, 2 H) 8.08 (s, 1 H) 7.70 - 7.77 (m, 2 H) 7.10 (d, 7=4.88 Hz, 1 H) 6.97 - 7.05 (m, 2 H) 4.84 (dd, 7=8.54, 1.53 Hz, 4 H) 4.23 - 4.27 (m, 1 H) 2.75 (d, 7=10.99 Hz, 2 H) 2.18 - 2.29 (m, 4 H) 2.04 (s, 1 H) 1.94 - 2.02 (m, 2 H) 1.77 - 1.90 (m, 2 H) 1.65 - 1.76 (m, 2 H) 1.42
- 1.59 (m, 4 H) 1.17 - 1.32 (m, 2 H); MS (APCI(+)) m/e 420 (M+H)+.
Example 1412
N-(4-{ [l-(tetrahydrofuran-2-ylmethyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 429, substituting tetrahydrofuran-2-carbaldehyde for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)- lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4- yl)phenyl)isoindoline-2-carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.53 - 8.59 (m, 2 H) 8.07 (s, 1 H) 7.73 (d, 7=9.16 Hz, 2 H) 7.10 (d, 7=5.49 Hz, 1 H) 6.97 - 7.02 (m, 2 H) 4.80 - 4.87 (m, 4 H) 4.03 (d, 7=11.60 Hz, 1 H) 3.77 - 3.84 (m, 1 H) 3.61 - 3.69 (m, 1 H) 2.88 (d, 7=41.81 Hz, 2 H) 2.25 - 2.63 (m, 4 H) 1.97 (s, 2 H) 1.77 - 1.91 (m, 4 H) 1.64
- 1.76 (m, 2 H) 1.44 - 1.58 (m, 1 H); MS (APCI(+)) m/e 423 (M+H)+.
Example 1413
N-(4- { [ 1 -(2-methylpropyl)piperidin-4-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 429, substituting isobutyraldehyde for isobutyraldehyde and N-(4-(piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4- c]pyridine-2(3H)-carboxamide for N-(4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl)isoindoline-2- carboxamide. ¾ NMR (400 MHz, Pyridine-^. Temp=90°C) δ ppm 8.49 - 8.60 (m, 2 H) 8.09 (s, 1 H) 7.68 - 7.80 (m, 2 H) 7.10 (d, 7=5.19 Hz, 1 H) 6.96 - 7.04 (m, 2 H) 4.85 (s, 4 H) 4.21 - 4.28 (m, 1 H) 2.65 - 2.79 (m, 2 H) 2.13 - 2.24 (m, 2 H) 2.06 (m, 2 H) 1.98 (s, 2 H) 1.77 - 1.88 (m, 2 H) 1.67 - 1.77 (m, 1 H) 0.89 (d, 7=6.71 Hz, 6 H); MS (APCI(+)) m/e 395 (M+H)+.
Example 1414
N-(4-{ [l-(butylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide
The tide compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline -2-carboxamide and 1-butylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.59 (s, 1 H) 8.49 (d, 7=4.88 Hz, 1 H) 7.36 - 7.48 (m, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.80 (d, 7=6.10 Hz, 4 H) 4.39 - 4.50 (m, 1 H) 3.41 - 3.49 (m, 2 H) 3.13 - 3.20 (m, 2 H) 2.99 - 3.06 (m, 2 H) 1.94 - 2.01 (m, 2 H) 1.63 - 1.76 (m, 4 H) 1.37 - 1.49 (m, 2 H) 0.91 (t, 7=7.48 Hz, 3 H); MS (APCI(+)) m/e 459 (M+H) +.
Example 1415
N-(4-{ [l-(cyclopropylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline -2-carboxamide and cyclopropylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.57 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.40 (d, 7=8.54 Hz, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=8.24 Hz, 4 H) 4.39 - 4.49 (m, 1 H) 3.44 - 3.51 (m, 2 H) 3.17 - 3.23 (m, 2 H) 2.54 - 2.58 (m, 1 H) 1.95 - 2.03 (m, 2 H) 1.68 - 1.78 (m, 2 H) 0.91 - 1.07 (m, 4 H); MS (APCI(+)) m/e 442 (M+H)+.
Example 1416
N-(4-{ [l-(phenylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline -2-carboxamide and phenylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.59 (s, 1 H) 8.49 (d, 7=4.88 Hz, 1 H) 7.77 (d, 7=7.32 Hz, 2 H) 7.71 (t, 7=7.32 Hz, 1 H) 7.65 (t, 7=7.32 Hz, 2 H) 7.44 (d, 7=4.88 Hz, 1 H) 7.35 (d, 7=8.85 Hz, 2 H) 6.79 (d, 7=9.16 Hz, 2 H) 4.79 (d, 7=4.27 Hz, 4 H) 4.29 - 4.37 (m, 1 H) 3.22 - 3.25 (m, 2 H) 2.92 - 3.06 (m, 2 H) 1.87 - 2.04 (m, 2 H) 1.61 - 1.79 (m, 2 H); MS (APCI(+)) m/e 479 (M+H)+. Example 1417
N- [4-( { 1 - [(4-fluorophenyl)sulfonyl]piperidin-4-yl } oxy)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline-2-carboxamide and (4-fluorophenyl)sulf nyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.58 (s, 1 H) 8.49 (d, 7=4.88 Hz, 1 H) 7.84 (dd, 7=8.85, 5.19 Hz, 2 H) 7.40 - 7.49 (m, 3 H) 7.36 (d, 7=8.85 Hz, 2 H) 6.80 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=4.88 Hz, 4 H) 4.28 - 4.41 (m, 1 H) 3.21 - 3.26 (m, 2 H) 2.94 - 3.05 (m, 2 H) 1.89 - 2.02 (m, 2 H) 1.62 - 1.76 (m, 2 H); MS (APCI(+)) m/e 497 (M+H)+.
Example 1418
N-(4-{ [l-(ethylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4-
(piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline-2-carboxamide and ethylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.58 (s, 1 H) 8.48 (d, 7=5.19 Hz, 1 H) 7.40 (d, 7=8.85 Hz, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=7.32 Hz, 4 H) 4.39 - 4.48 (m, 1 H) 3.41 - 3.49 (m, 2 H) 3.14 - 3.22 (m, 2 H) 3.05 (q, 7=7.43 Hz, 2 H) 1.94 - 2.03 (m, 2 H) 1.64 - 1.78 (m, 2 H) 1.24 (t, 7=7.32 Hz, 3 H); MS (APCI(+)) m/e 431 (M+H)+.
Example 1419
N-(4-{ [l-(propan-2-ylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline-2-carboxamide and isopropylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.59 (s, 1 H) 8.49 (d, 7=5.19 Hz, 1 H) 7.36 - 7.47 (m, 3 H) 6.89 (d, 7=8.85 Hz, 2 H) 4.80 (d, 7=5.49 Hz, 4 H) 4.40 - 4.49 (m, 1 H) 3.46 - 3.55 (m, 2 H) 3.33 - 3.36 (m, 1 H) 3.15 - 3.24 (m, 2 H) 1.93 - 2.01 (m, 2 H) 1.62 - 1.74 (m, 2 H) 1.25 (d, 7=6.71 Hz, 6 H); MS (APCI(+)) m/e 445 (M+H)+.
Example 1420
N-(4-{ [l-(benzylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2-carboxamide The title compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for N-(4- aminophenyl)isoindoline-2-carboxamide and benzylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.58 (s, 1 H) 8.48 (d, 7=4.88 Hz, 1 H) 7.31 - 7.46 (m, 8 H) 6.87 (d, 7=9.16 Hz, 2 H) 4.79 (d, 7=7.02 Hz, 4 H) 4.38 - 4.44 (m, 1 H) 4.36 (s, 2 H) 3.34 - 3.38 (m, 2 H) 3.07 - 3.16 (m, 2 H) 1.82 - 1.90 (m, 2 H) 1.57 - 1.71 (m, 2 H);MS (APCI(+)) m/e 493 (M+H)+.
Example 1421
N-(4-{ [l-(propylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline -2-carboxamide and 1-propylsulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.59 (s, 1 H) 8.49 (d, 7=4.88 Hz, 1 H) 7.35 - 7.46 (m, 3 H) 6.90 (d, 7=8.85 Hz, 2 H) 4.80 (d, 7=5.80 Hz, 4 H) 4.39 - 4.48 (m, 1 H) 3.39 - 3.49 (m, 2 H) 3.12 - 3.22 (m, 2 H) 2.96 - 3.06 (m, 2 H) 1.93 - 2.03 (m, 2 H) 1.62 - 1.79 (m, 4 H) 1.01 (t, 7=7.48 Hz, 3 H); MS (APCI(+)) m/e 445 (M+H)+.
Example 1422
N-(4-{ [l-(thiophen-2-ylsulfonyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 883, substituting N-(4- (piperidin-4-yloxy)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide for N-(4- aminophenyl)isoindoline -2-carboxamide and thiophene-2-sulfonyl chloride for (3- methoxyphenyl)methanesulfonyl chloride. ¾ NMR (400 MHz, DMSO-D20, Temp=90°C) δ ppm 8.58 (s, 1 H) 8.49 (d, 7=5.19 Hz, 1 H) 7.96 (d, 7=4.27 Hz, 1 H) 7.63 (d, 7=3.05 Hz, 1 H) 7.44 (d, 7=4.88 Hz, 1 H) 7.37 (d, 7=8.85 Hz, 2 H) 7.23 - 7.30 (m, 1 H) 6.81 (d, 7=8.85 Hz, 2 H) 4.79 (d, 7=4.88 Hz, 4 H) 4.29 - 4.43 (m, 1 H) 3.31 - 3.38 (m, 2 H) 2.97 - 3.09 (m, 2 H) 1.93 - 2.06 (m, 2 H) 1.65 - 1.81 (m, 2 H); MS (APCI(+)) m/e 485 (M+H)+.
Example 1441
benzyl trans-3-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] cyclobutanecarboxylate
Example 1441 A
benzyl trans-3-(tert-butoxycarbonylamino)cyclobutanecarboxylate A suspension of trans-3-(tert-butoxycarbonylamino)cyclobutanecarboxylic acid (0.5 g, 2.323 mmol) and potassium carbonate (0.321 g, 2.323 mmol) in dimethylformamide (2.323 ml) was treated with (bromomethyl)benzene (0.401 g, 2.346 mmol) added from a syringe over 3 minutes. The reaction mixture was stirred at room temperature for 17 hours and water was added. The suspension was filtered and the solid collected was washed with water and dried under vacuum to give the title compound.
Example 144 IB
trans-benzyl 3-aminocyclobutanecarboxylate
The title compound was prepared as described in Example 2D, substituting benzyl trans-3-(tert-butoxycarbonylamino)cyclobutanecarboxylate for tert-butyl 4-((4-(5- fluoroisoindoline-2 carboxamido)benzamido)methyl)benzylcarbamate.
Example 1441C
benzyl trans-3-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] cyclobutanecarboxylate
The title compound was prepared as described in Example 272B, substituting trans- benzyl 3-aminocyclobutanecarboxylate for 4-amino-N-propylbenzamide and l,3-dihydro-2H- pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate hydrochloride. ¾ NMR (300
MHz, DMSO-de) δ ppm 8.56 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 7.43 - 7.31 (m, 6H), 6.68 (d, J = 7.6 Hz, 1H), 5.14 (s, 2H), 4.65 - 4.58 (m, 4H), 4.41 - 4.29 (m, 1H), 3.11 - 2.99 (m, 1H), 2.46 - 2.25 (m, 4H); MS (ESI(+)) m/e 352 (M+H)+.
Example 1452
N-(4-{3-[(3-methylbutanoyl)amino]oxetan-3-yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
Example 1452 A
2-methyl-N-(oxetan-3-ylidene)propane-2-sulfin amide To a 250 mL round-bottomed flask was added 2-methylpropane-2-sulfinamide (3.36 g, 27.8 mmol) followed by tetraethoxytitanium (11.64 ml, 55.5 mmol) to a tetrahydrofuran (69.4 ml) solution of oxetan-3-one (2 g, 27.8 mmol) at room temperature. The mixture was stirred at 50°C for 5 hours, cooled and poured into brine. The suspension was filtered through a pad of diatomaceous earth eluting with ethyl acetate. The organics were combined, dried with sodium sulfate, filtered and concentrated under vacuum. The residue was purified by regular phase flash column chromatography to give the title compound.
Example 1452B
N-(3-(4-bromophenyl)oxetan-3-yl)-2-methylpropane-2-sulfinamide To a 50 mL round-bottomed flask was added 1,4-dibromobenzene (2.85 g, 12.07 mmol) in tetrahydrofuran (40.2 ml). The solution was cooled to -78°C and n-butyl lithium (4.51 ml, 11.26 mmol) was added dropwise. The mixture was stirred for 1 hour at -78°C. 2- methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (1.41 g, 8.05 mmol) was added as a tetrahydrofuran solution (ca 1 ml) and the reaction was stirred for 10 minutes and warmed to room temperature. Saturated ammonium chloride was added followed by water and dichloromethane. The aqueous layer was extracted twice with dichloromethane and the combined organics were dried with magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by regular phase, flash column chromatography to give the title compound.
Example 1452C
N-(4-(3-(l,l-dimethylethylsulfinamido)oxetan-3-yl)phenyl)acetamide To a 5 mL microwave tube was added N-(3-(4-bromophenyl)oxetan-3-yl)-2- methylpropane-2-sulfinamide (436 mg, 1.312 mmol), cesium carbonate (1283 mg, 3.94 mmol), and acetamide (116 mg, 1.968 mmol) in dioxane (6.5 ml). Xantphos (76 mg, 0.131 mmol) and tris(dibenzylideneacetone)dipalladium(0) (60.1 mg, 0.066 mmol) were added; the tube was flushed with nitrogen and capped. The mixture was heated at 100°C for 45 minutes. Aqueous work up with dichloromethane extraction gave an organic layer that was dried with sodium sulfate, filtered and concentrated under vacuum. Regular phase chromatography provided the title compound.
Example 1452D
N-(3-(4-aminophenyl)oxetan-3-yl)-2-methylpropane-2-sulfinarnide Claisen's alkali (potassium hydroxide, 12.7 g in 9 ml water and 33 ml methanol) was added to N-(4-(3-(l,l-dimethylethylsulfinamido)oxetan-3-yl)phenyl)acetamide (300 mg, 0.966 mmol) and the reaction was stirred at 90°C for 2 hours. The mixture was cooled to room temperature when water and ethyl acetate were added. The aqueous layer was extracted twice with ethyl acetate and the combined organics were dried with magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by regular phase flash column chromatography to give the title compound.
Example 1452E
N-(4-(3-(l,l-dimethylethylsulfinamido)oxetan-3-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-
2(3H)-carboxamide
The title compound was prepared as described in Example 272B, substituting N-(3- (4-aminophenyl)oxetan-3-yl)-2-methylpropane-2-sulfinamide for 4-amino-N- propylbenzamide and l,3-dihydro-2H-pyrrolo[3,4-c]pyridine for methyl isoindoline-5- carboxylate hydrochloride.
Example 1452F
N-(4-(3-aminooxetan-3-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide In a 20 mL vial was added N-(4-(3-(l,l-dimethylethylsulfinamido)oxetan-3- yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide (253 mg, 0.610 mmol) and methanol (6.1 ml). 4N HCl in dioxane (229 μΐ, 0.916 mmol) was added and the reaction was stirred for 2 hours. The mixture was concentrated under vacuum to give the title compound which was used without further purification.
Example 1452G
N-(4-{3-[(3-memylbutanoyl)amino]oxetan-3-yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4-(3- aminooxetan-3-yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide for 3- phenylpropan-1 -amine and 3-methylbutanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.61 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.44 (s, 1H), 7.54 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 4.8 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H), 4.81 (d, J = 6.5 Hz, 6H), 4.69 (d, J = 6.5 Hz, 2H), 2.10 - 1.87 (m, 3H), 0.90 (d, J = 6.4 Hz, 6H); MS (ESI(+)) m/e 395 (M+H)+.
Example 1453
tert-butyl 4-({4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino]phenyl } sulfonyl)piperidine- 1 -carboxylate
Example 1453 A
tert-butyl 4-(4-aminophenylthio)piperidine- 1 -carboxylate To a 100 mL round-bottomed flask was added 4-aminobenzenethiol (4.9 g, 39.1 mmol) and potassium carbonate (9.72 g, 70.3 mmol) in dimethylformamide (20 ml), tert- Butyl 4-(tosyloxy)piperidine-l -carboxylate (5 g, 14.07 mmol) was added and the reaction was stirred in a sealed flask at 70°C for 20 hours. The mixture was cooled and filtered through a plug of silica gel with dichloromethane. The filtrate was concentrated under vaccum and chromatographed to give the title compound.
Example 1453B
tert-butyl 4-(4-acetamidophenylthio)piperidine-l -carboxylate
To a 10 mL round -bottomed flask was added tert-butyl 4-(4- aminophenylthio)piperidine-l -carboxylate (100 mg, 0.324 mmol) and triethylamine (249 μΐ, 1.783 mmol) in dichloromethane (3242 μΐ). The mixture was cooled to -78°C and acetyl chloride (115 μΐ, 1.621 mmol) was added. The solution was warmed to room temperature, stirred for 1 h and then diluted with water and additional dichloromethane. The aqueous phase was extracted twice with dichloromethane and the combined organics were dried with sodium sulfate, filtered and concentrated to give the title compound.
Example 1453C
tert-butyl 4-(4-acetamidophenylsulfonyl)piperidine- 1 -carboxylate In a 10 mL round-bottomed flask was added tert-butyl 4-(4- acetamidophenylthio)piperidine-l -carboxylate (100 mg, 0.285 mmol) in dichloromethane (2.9 ml). The solution was cooled to -20°C and mCPBA (192 mg, 0.856 mmol) was added. The reaction mixture was allowed to warm to room temperature and treated with IN aqueous NaOH. The aqueous layer was extracted with dichloromethane and the combined organics were dried with sodium sulfate, filtered and concentrated to give the title compound.
Example 1453D
tert-butyl 4-(4-aminophenylsulfonyl)piperidine-l-carboxylate
The title compound was prepared as described in Example 1452D, substituting tert- butyl 4-(4-acetamidophenylsulfonyl)piperidine-l-carboxylate for N-(4-(3-(l,l- dimethylethylsulfinamido)oxetan-3-yl)phenyl)acetamide.
Example 1453E
tert-butyl 4-({4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl)amino]phenyl } sulfonyl)piperidine- 1 -carboxylate The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(4-aminophenylsulfonyl)piperidine-l -carboxylate for 4-amino-N-propylbenzamide and l,3-dihydro-2H-pyrrolo[3,4-c]pyridine for methyl isoindoline-5-carboxylate. ¾ NMR (300 MHz, DMSO-d6) δ 8.95 (s, 1H), 8.62 (s, 1H), 8.51 (d, 7 = 5.0 Hz, 1H), 7.90 - 7.83 (m, 2H), 7.76 - 7.69 (m, 2H), 7.44 (d, J = 5.1 Hz, 1H), 4.93 - 4.76 (m, 4H), 4.09 - 3.93 (m, 2H), 2.84 - 2.56 (m, 1H), 1.83 (d, 7 = 10.8 Hz, 1H), 1.48 - 1.16 (m, 6H); MS (ESI(+)) m/e 431 (M+H)+.
Example 1454
N- { 4- [4-(propylcarbamoyl)piperidin- 1 -yfjphenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide
Example 1454 A
l-(4-(2,3-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxarnido)phenyl)piperidine-4-carboxylic acid
The title compound was prepared as described in Example 1246, substituting methyl piperidine-4-carboxylate for methyl azetidine-3 -carboxylate hydrochloride in Example 1246 A.
Example 1454B
N- {4-[4-(propylcarbamoyl)piperidin- 1 -yfjphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 1C, substituting propan-1- amine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2- carboxamido)phenyl)piperidine-4-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- ) δ ppm 8.60 (s, 1H), 8.49 (d, 7 = 5.0 Hz, 1H), 8.19 (s, 1H), 7.77 (t, 7 = 5.6 Hz, 1H), 7.42 (d, 7 = 5.1 Hz, 1H), 7.39 - 7.33 (m, 2H), 6.89 - 6.83 (m, 2H), 4.77 (d, 7 = 6.2 Hz, 4H), 3.64 - 3.56 (m, 2H), 3.05 - 2.94 (m, 2H), 2.63 - 2.52 (m, 2H), 2.28 - 2.14 (m, 1H), 1.79 - 1.59 (m, 4H), 1.47 - 1.33 (m, 2H), 0.84 (t, 7 = 7.4 Hz, 3H); MS (ESI(+)) m/e 408 (M+H)+.
Table 23.
The following examples were essentially prepared as described in Example 1C, 5 substituting the appropriate amine for 3-phenylpropan-l -amine and l-(4-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)piperidine-4-carboxylic acid for 4-(isoindoline-
2-carboxamido)benzoic acid.
Figure imgf000901_0001
c]pyridine-2- 2H), 2.29 - 2.18 (m, 1H), 1.78 - 1.56 (m, 5H), 1.57 - 1.47 carboxamide (m, 2H), 1.20 - 1.06 (m, 2H)
1462 N-{4-[4- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.60 (s, 1H), 8.49 (d, 7 (ESI(+))
(cyclopropylcarbamoyl)p = 5.0 Hz, 1H), 8.19 (s, 1H), 7.84 (d, 7 = 4.3 Hz, 1H), 7.42 (d, m/e 406 iperidin- 1 -yl] phenyl } - 7 = 5.1 Hz, 1H), 7.39 - 7.33 (m, 2H), 6.89 - 6.83 (m, 2H), (M+H)+ l,3-dihydro-2H- 4.80 - 4.74 (m, 4H), 3.63 - 3.55 (m, 2H), 2.66 - 2.48 (m,
pyrrolo[3,4-c]pyridine-2- 3H), 2.20 - 2.08 (m, 1H), 1.76 - 1.58 (m, 4H), 0.63 - 0.55
carboxamide (m, 2H), 0.41 - 0.33 (m, 2H)
1463 N-(4-{4- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.59 (s, 1H), 8.49 (d, 7 (ESI(+))
[(tetrahydrofuran-3- = 5.0 Hz, 1H), 8.19 (s, 1H), 7.91 (t, 7 = 5.7 Hz, 1H), 7.42 (d, 7 m/e 450 ylmethyl)carbamoyl]pipe = 4.5 Hz, 1H), 7.39 - 7.33 (m, 2H), 6.89 - 6.83 (m, 2H), 4.80 (M+H)+ ridin- 1-yl jphenyl)- 1,3- - 4.74 (m, 4H), 3.73 - 3.54 (m, 5H), 3.40 - 3.34 (m, 1H),
dihydro-2H-pyrrolo[3,4- 3.09 - 2.98 (m, 2H), 2.64 - 2.53 (m, 2H), 2.37 - 2.27 (m,
c]pyridine-2- 1H), 2.27 - 2.17 (m, 1H), 1.94 - 1.83 (m, 1H), 1.79 - 1.61
carboxamide (m, 4H), 1.57 - 1.46 (m, 1H)
1464 N-(4-{4-[(2-hydroxy-2- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.60 (s, 1H), 8.49 (d, 7 (ESI(+)) methylpropyl)carbamoyl = 5.0 Hz, 1H), 8.19 (s, 1H), 7.66 (t, 7 = 6.0 Hz, 1H), 7.42 (d, 7 m/e 438
]piperidin- 1 -yl jphenyl)- = 4.6 Hz, 1H), 7.39 - 7.33 (m, 2H), 6.90 - 6.83 (m, 2H), 4.83 (M+H)+ l,3-dihydro-2H- - 4.71 (m, 4H), 4.44 (s, 1H), 3.65 - 3.57 (m, 2H), 3.03 (d, 7 = pyrrolo[3,4-c]pyridine-2- 6.0 Hz, 2H), 2.64 - 2.53 (m, 2H), 2.39 - 2.27 (m, 1H), 1.79 - carboxamide 1.61 (m, 4H), 1.04 (s, 6H)
1465 N-{4-[4-(butan-2- ¾ NMR (400 MHz, DMSO- ) δ ppm 8.60 (s, 1H), 8.49 (d, 7 (ESI(+)) ylcarbamoyl)piperidin- 1 - = 5.0 Hz, 1H), 8.19 (s, 1H), 7.56 (d, 7 = 8.2 Hz, 1H), 7.42 (d, m/e 422 y 1] phenyl } - 1 , 3 -dihydro - 7 = 4.5 Hz, 1H), 7.39 - 7.33 (m, 2H), 6.89 - 6.83 (m, 2H), (M+H)+ 2H-pyrrolo[3,4- 4.81 - 4.70 (m, 4H), 3.72 - 3.54 (m, 3H), 2.62 - 2.50 (m,
c]pyridine-2- 2H), 2.27 - 2.14 (m, 1H), 1.78 - 1.58 (m, 4H), 1.44 - 1.28
carboxamide (m, 2H), 1.01 (d, 7 = 6.6 Hz, 3H), 0.81 (t, 7 = 7.4 Hz, 3H)
Example 1472
N-(4- { (4R)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
A racemic mixture of N-(4-{4-[(2-methylpropanoyl)amino]cyclohex-l-en-l- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide (250 mg) was dissolved in methanol and separated using SCF-LC with a ChiralPak AD-H 21x250mm column to provide N-(4- { (4R)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.61 (s, 1H), 8.50
(d, 7 = 5.0 Hz, 1H), 8.41 (s, 1H), 7.66 (d, 7 = 7.6 Hz, 1H), 7.56 - 7.48 (m, 2H), 7.43 (d, 7 =
5.1 Hz, 1H), 7.37 - 7.29 (m, 2H), 6.02 (bs, 1H), 4.84 - 4.77 (m, 4H), 3.89 - 3.73 (m, 1H),
2.44 (ddd, 7 = 12.7, 8.7, 4.6 Hz, 2H), 2.41 - 2.26 (m, 2H), 2.14 - 1.97 (m, 1H), 1.93 - 1.81
(m, 1H), 1.67 - 1.49 (m, 1H), 1.00 (dd, 7 = 6.8, 2.4 Hz, 6H); MS (ESI(+)) m/e 405 (M+H)+.
Example 1473
N-(4- { (4S)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
A racemic mixture of N-(4-{4-[(2-methylpropanoyl)amino]cyclohex-l-en-l- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide (250 mg) was dissolved in methanol and separated using SCF-LC with a ChiralPak AD-H 21x250mm column to provide N-(4- { (4S)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.61 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.41 (s, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.56 - 7.49 (m, 2H), 7.43 (d, J = 5.1 Hz, 1H), 7.37 - 7.29 (m, 2H), 6.05 - 5.99 (m, 1H), 4.84 - 4.77 (m, 4H), 3.89 - 3.73 (m, 1H), 2.47 - 2.39 (m, 1H), 2.41 - 2.30 (m, 2H), 2.11 - 1.97 (m, 1H), 1.93 - 1.82 (m, 1H), 1.67 - 1.50 (m, 1H), 1.00 (dd, J = 6.8, 2.4 Hz, 6H); MS (ESI(+)) m/e 405 (M+H)+.
Example 1474
N-[4-( 1 -benzoylazetidin-3 -yl)butyl] - 1 ,3 -dihydro-2H-isoindole-2-carboxamide
Example 1474 A
tert-butyl 3-(2-hydroxyethyl)azetidine-l-carboxylate
A solution of 2-(l-(tert-butoxycarbonyl)azetidin-3-yl)acetic acid (1 g, 4.65 mmol) in tetrahydrofuran (5 ml) was cooled to 0°C and treated with borane tetrahydrofuran complex (7.00 ml, 7 mmol) dropwise by syringe. After 1 hour at 0°C the solution was allowed to warm to room temperature and stirred overnight and then it was quenched with 20 ml of 1M aqueous NaOH. The separated aqueous layer was extracted with ether (2 x 15 ml), dried with magnesium sulfate, filtered and concentrated to give the title compound which was used without purification.
Example 1474B
tert-butyl 3-(2-oxoethyl)azetidine-l -carboxylate To a solution of oxalyl chloride (488 μΐ, 5.58 mmol) in 40 ml dichloromethane at
-78°C was added dimethyl sulfoxide (792 μΐ, 11.16 mmol) dropwise by syringe. The mixture was stirred for 15 minutes at -78°C when a solution of tert-butyl 3-(2-hydroxyethyl)azetidine- 1-carboxylate (936 mg, 4.65 mmol) in 10 ml dichloromethane was added dropwise by syringe. After 1 hour at -78°C, triethylamine (3241 μΐ, 23.25 mmol) was added and the suspension was warmed to room temperature and stirred for an additional hour. The mixture was quenched with water (25 ml) and saturated aqueous potassium carbonate (10 ml), stirred vigorously and separated. The aqueous layer was extracted with dichloromethane (2 x 20 ml) and the combined organic layers were dried with magnesium sulfate, filtered and concentrated. The crude material was flash chromatographed to give the title compound.
Example 1474C
tert-butyl 3-(3-cyanoallyl)azetidine- 1 -carboxylate To a solution of potassium tert-butoxide, 1M in tetrahydrofuran (3694 μΐ, 3.69 mmol) at 0°C was added dropwise by syringe a solution of diethyl cyanomethylphosphonate (570 μΐ, 3.52 mmol) in 5 ml tetrahydrofuran. The reaction mixture was warmed to room temperature and then cooled to 0°C again. This solution was treated with tert-butyl 3-(2- oxoethyl)azetidine-l -carboxylate (701 mg, 3.52 mmol) in 2 ml tetrahydrofuran dropwise by syringe and then allowed to warm to room temperature. After stirring overnight the gelatinous mixture was quenched with water (20 ml) and extracted with ethyl acetate (2 x 20 ml); the organic layers were washed with brine (20 ml), dried with magnesium sulfate, filtered and concentrated. The liquid residue was flash chromatographed to give the title compound as a 1 : 1 mixture of E/Z isomers.
Example 1474D
tert-butyl 3-(4-aminobutyl)azetidine-l -carboxylate 7M NH3-CH3OH (10 mL) was added to tert-butyl 3-(3-cyanoallyl)azetidine-l- carboxylate (640 mg, 2.88 mmol) and Ra-Ni 2800, water slurry (881 mg, 6.75 mmol) in a 20 mL pressure bottle. The mixture was stirred under 30 psi of hydrogen at room temperature for 16 hours. The mixture was filtered through a polypropylene membrane, concentrated by rotovap and dried under vacuum to provide the title compound which was used without purification.
Example 1474E
tert-butyl 3-(4-(isoindoline-2-carboxamido)butyl)azetidine- 1 -carboxylate
The title compound was prepared as described in Example 344A, substituting tert- butyl 3-(4-aminobutyl)azetidine-l-carboxylate for tert-butyl 5-aminoisoindoline-2- carboxylate.
Example 1474F
N-(4-(azetidin-3-yl)butyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl
3-(4-(isoindoline-2-carboxamido)butyl)azetidine-l -carboxylate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate.
Example 1474G
N- [4-( 1 -benzoylazetidin-3 -yl)butyl] - 1 ,3 -dihydro-2H-isoindole-2-carboxamide The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(4-(azetidin-3-yl)butyl)isoindoline-2-carboxamide for 5- amino-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 7.67 - 7.57 (m, 2H), 7.57 - 7.39 (m, 3H), 7.39 - 7.23 (m, 4H), 6.28 (s, 1H), 4.56 (s, 4H), 4.34 (t, J = 8.3 Hz, 1H), 4.11 (t, 7 = 9.0 Hz, 1H), 4.01 - 3.82 (m, 1H), 3.65 (dd, 7 = 9.8, 5.8 Hz, 1H), 3.07 (dd, J = 12.7, 6.8 Hz, 2H), 2.66 - 2.53 (m, 1H), 1.59 (dd, 7 = 15.3, 7.7 Hz, 2H), 1.51 - 1.36 (m, 2H), 1.25 (dd, 7 = 13.5, 6.4 Hz, 2H); MS (ESI(+)) m/e 378 (M+H)+.
Example 1475
N- [4-(l-benzoylazetidin-3-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide
Example 1475 A
tert-butyl 3-(4-(2,3-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)butyl)azetidine-l- carboxylate The title compound was prepared as described in Example 344A, substituting tert- butyl 3-(4-aminobutyl)azetidine-l-carboxylate for tert-butyl 5-aminoisoindoline-2- carboxylate and l,3-dihydro-2H-pyrrolo[3,4-c]pyridine for isoindoline.
Example 1475B
N-(4-(azetidin-3-yl)butyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide
The title compound was prepared as described in Example 2D, substituting tert-butyl 3-(4-(23-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)butyl)azetidine-l-carboxylate for tert-butyl 4-((4-(5-fluoroisoindoline-2-carboxarnido)benzamido)methyl)benzylcarbamate.
Example 1475C
N-[4-(l-benzoylazetidin-3-yl)butyl]-13-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide The title compound was prepared as described in Example 278, substituting benzoyl chloride for acetyl chloride and N-(4-(azetidin-3-yl)butyl)- lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 5-arrdno-N-(4-(propylcarbamoyl)phenyl)isoindoline-2-carboxarnide. ¾ NMR (300 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 7.67 - 7.55 (m, 2H), 7.55 - 7.34 (m, 4H), 6.37 (t, J = 5.5 Hz, 1H), 4.60 (d, J = 2.3 Hz, 4H), 4.35 (t, J = 8.3 Hz,
1H), 4.11 (t, J = 9.1 Hz, 1H), 3.96 - 3.83 (m, 1H), 3.65 (dd, J = 9.7, 5.7 Hz, 1H), 3.07 (dd, J = 12.8, 6.7 Hz, 2H), 2.65 - 2.53 (m, 1H), 1.59 (dd, J = 15.2, 7.6 Hz, 2H), 1.43 (dd, 7 = 14.4, 7.2 Hz, 2H), 1.34 - 1.09 (m, 2H); MS (ESI(+)) m/e 379 (M+H)+.
Example 1476
N- [trans-3-(benzylcarbamoyl)cyclobutyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide
Example 1476 A
trans-3-(2,3-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxarnido)cyclobutanecarboxylic acid The title compound was prepared as described in Example 272A, substituting benzyl trans-3-[(l,3-dmydro-2H-pyrrolo[3,4-c]pyridin-2-ylcarbonyl)arnino]cyclobutanecarboxylate for 4-nitro-N-propylbenzamide.
Example 1476B
N- [trans-3-(benzylcarbamoyl)cyclobutyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide
The title compound was prepared as described in Example 1C, substituting benzylamine for 3-phenylpropan-l -amine and trans-3-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)cyclobutanecarboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.56 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 8.26 (t, J = 5.9 Hz, 1H), 7.39 (d, J = 5.1 Hz, 1H), 7.36 - 7.28 (m, 2H), 7.27 - 7.20 (m, 3H), 6.60 (d, J = 1.6 Hz, 1H), 4.65 - 4.59 (m, 4H), 4.45 - 4.29 (m, 1H), 4.28 (d, J = 5.9 Hz, 2H), 2.96 - 2.84 (m, 1H), 2.41 - 2.29 (m, 2H), 2.30 - 2.15 (m, 2H); MS (ESI(+)) m/e 351 (M+H)+. Example 1477
N- { trans-3- [(2-phenylethyl)carbamoyl]cyclobutyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide
The tide compound was prepared as described in Example 1C, substituting 2- phenylethylamine for 3-phenylpropan-l -amine and trans-3-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)cyclobutanecarboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.56 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 7.80 (t, 7 = 5.6 Hz, 1H), 7.39 (d, 7 = 5.1 Hz, 1H), 7.33 - 7.24 (m, 2H), 7.23 - 7.16 (m, 3H), 6.57 (d, 7 = 7.6 Hz, 1H), 4.65 - 4.58 (m, 4H), 4.38 - 4.24 (m, 1H), 3.33 - 3.23 (m, 2H), 2.84 - 2.74 (m, 1H), 2.72 (t, J = 7.3 Hz, 2H), 2.32 - 2.22 (m, 2H), 2.24 - 2.09 (m, 2H); MS (ESI(+)) m/e 365 (M+H)+.
Example 1478
N-{trans-3-[(3-phenylpropyl)carbamoyl]cyclobutyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-
2-carboxamide
The title compound was prepared as described in Example 1C, substituting 3- phenylpropylamine for 3-phenylpropan-l -amine and trans-3-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)cyclobutanecarboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (400 MHz, DMSO- ) δ ppm 8.56 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 7.75 (t, 7 = 5.5 Hz, 1H), 7.38 (d, 7 = 5.1 Hz, 1H), 7.32 - 7.24 (m, 2H), 7.24 - 7.13 (m, 3H), 6.58 (d, 7 = 7.6 Hz, 1H), 4.66 - 4.55 (m, 4H), 4.41 - 4.27 (m, 1H), 3.11 - 3.03 (m, 2H), 2.89 - 2.75 (m, 1H), 2.62 - 2.52 (m, 2H), 2.39 - 2.25 (m, 2H), 2.26 - 2.11 (m, 2H), 1.76 - 1.63 (m, 2H); MS (ESI(+)) m/e 379 (M+H)+.
Example 1525
N-[4-(cis-4-{ [(2-methoxyethoxy)acetyl] amino }cyclohexyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
Example 1525 A
tert-butyl 4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2- carboxamido)phenyl)cyclohexylcarbamate
The title compound was prepared as described in Example 979A, substituting tert- butyl 4-(4-(2,3-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxarnido)phenyl)cyclohex-3- enylcarbamate for tert-Butyl 4-(4-(isoindoline-2-carboxamido)phenyl)-5,6-dihydropyridine- 1 (2H)-carboxylate.
Example 1525B
N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxarnide The title compound was prepared as described in Example 2D, substituting tert-butyl
4-(4-(2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)phenyl)cyclohexylcarbamate for tert-butyl 4-((4-(5-fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate. Example 1525C
N-[4-(cis-4- { [(2-methoxyethoxy)acetyl] amino }cyclohexyl)phenyl]- l ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 : 1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and 2-(2-methoxyethoxy)acetic acid for 4- (isoindoline-2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N- [4-(cis-4- { [(2 -methoxyethoxy) acetyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (501 MHz, DMSO-d6) δ 8.59 (bs, 1H), 8.51 - 8.45 (m, 1H), 8.32 (bs, 1H), 7.44 (dd, J = 11.5, 5.2 Hz, 3H), 7.40 (t, J = 7.6 Hz, 1H), 7.17 - 7.11 (m, 2H), 4.81 - 4.74 (m, 4H), 4.03 - 3.96 (m, 1H), 3.90 (d, J = 2.2 Hz, 2H), 3.63 - 3.58 (m, 2H), 3.52 - 3.46 (m, 2H), 3.27 - 3.23 (m, 3H), 1.80 - 1.30 (m, 8H); MS (ESI(+)) m/e 453 (M+H)+.
Example 1526
N-[4-(trans-4-{ [(2-methoxyethoxy)acetyl]amino }cyclohexyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 : 1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and 2-(2-methoxyethoxy)acetic acid for 4- (isoindoline-2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N- [4-(trans-4- { [(2-methoxyethoxy)acetyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (501 MHz, DMSO-d6) δ 8.58 (s, 1H), 8.48 (d, J = 5.0 Hz, 1H), 8.31 (s, 1H), 7.50 - 7.39 (m, 4H), 7.15 - 7.09 (m, 2H), 4.81 - 4.74 (m, 4H), 3.85 (s, 2H), 3.74 - 3.58 (m, 1H), 3.58 - 3.55 (m, 2H), 3.49 - 3.46 (m, 2H), 3.28 (s, 3H), 2.45 - 2.37 (m, 1H), 1.89 - 1.82 (m, 2H), 1.83 - 1.75 (m, 2H), 1.58 - 1.42 (m, 2H), 1.44 - 1.29 (m, 2H); MS (ESI(+)) m/e 453 (M+H)+.
Example 1527
N-[4-(cis-4-{ [(2S)-tetrahydrofuran-2-ylcarbonyl]amino }cyclohexyl)phenyl]- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 : 1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and (S)-tetrahydrofuran-2-carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-[4-(cis-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } eye lohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (501 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.48 (d, J = 5.0 Hz, 1H), 8.32 (s, 1H), 7.47 - 7.38 (m, 4H), 7.17 - 7.12 (m, 2H), 4.81 - 4.75 (m, 4H), 4.29 - 4.22 (m, 1H), 3.94 - 3.86 (m, 2H), 3.77 (t, 7 = 7.1 Hz, 1H), 2.14 - 2.02 (m, 1H), 1.88 - 1.78 (m, 3H), 1.70 (dd, J = 22.1, 8.6 Hz, 3H), 1.63 (t, J = 17.3 Hz, 6H); MS (ESI(+)) m/e 435 (M+H)+.
Example 1528
N-[4-(trans-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 :1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and (S)-tetrahydrofuran-2-carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N- [4-(trans-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (501 MHz, DMSO-d6) δ 8.58 (bs, 1H), 8.51 - 8.45 (m, 1H), 8.30 (bs, 1H), 7.53 - 7.45 (m, 1H), 7.42 (d, J = 8.3 Hz, 2H), 7.14 - 7.08 (m, 2H), 4.81 - 4.74 (m, 4H), 4.20 - 4.13 (m, 1H), 3.92 - 3.85 (m, 1H), 3.78 - 3.71 (m, 1H), 3.66 - 3.58 (m, 1H), 2.39 (s, 1H), 2.09 (dd, J = 10.8, 6.4 Hz, 1H), 1.79 (s, 7H), 1.62 (s, 1H), 1.45 (dd, J = 26.5, 15.7 Hz, 4H); MS (ESI(+)) m/e 435 (M+H)+.
Example 1529
N-[4-(cis-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 :1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and (R)-tetrahydrofuran-2-carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-[4-(cis-4-{ [(2R)-tetrahydrofuran-2-ylcarbonyl]arnino}cyclohexyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (501 MHz, DMSO-d6) δ 8.55 (t, J = 21.5 Hz, 1H), 8.46 (s, 1H), 8.32 (d, J = 9.4 Hz, 1H), 7.47 - 7.37 (m, 4H), 7.14 (bs, 2H), 4.77 (bs, 4H), 4.29 - 4.20 (m, 1H), 3.96 - 3.84 (m, 2H), 3.80 - 3.71 (m, 1H), 2.12 - 2.01 (m, 1H), 1.76 (d, J = 48.5 Hz, 4H), 1.60 (s, 7H); MS (ESI(+)) m/e 435 (M+H)+.
Example 1530
N-[4-(trans-4-{ [(2R)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 :1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and (R)-tetrahydrofuran-2-carboxylic acid for 4- (isoindoline-2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-[4-(trans-4-{ [(2R)-tetrahydrofuran-2-ylcarbonyl]arnino}cyclohexyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide. ¾ NMR (501 MHz, DMSO-d6) δ 8.58 (bs, 1H), 8.50 - 8.45 (m, 1H), 8.31 (bs, 1H), 7.52 - 7.46 (m, 1H), 7.45 - 7.39 (m, 3H), 7.14 - 7.08 (m, 2H), 4.81 - 4.74 (m, 4H), 4.20 - 4.13 (m, 1H), 3.92 - 3.84 (m, 1H), 3.78 - 3.70 (m, 1H), 3.66 - 3.57 (m, 1H), 2.43 - 2.34 (m, 1H), 2.14 - 2.02 (m, 1H), 2.04 - 1.52 (m, 7H), 1.54 - 1.24 (m, 4H); MS (ESI(+)) m/e 435 (M+H)+.
Example 1531
N-(6-{ [(2S)-tetrahydrofuran-2-ylmemyl]carbamoyl}pyridazin-3-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
Example 1531 A
methyl 6-(23-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylate Methyl 6-aminopyridazine-3-carboxylate (2 g, 13.06 mmol) was suspended in dichloromethane (50 ml) followed by addition of dry pyridine (1.265 ml, 15.67 mmol) under nitrogen. To this suspension was added a dichloromethane solution of 4-nitrophenyl carbonochloridate (2.99 g, 14.37 mmol) via syringe at ambient temperature. The mixture was stirred overnight to give a suspension that was concentrated to half volume under a stream of nitrogen. 2,3-Dihydro-lH-pyrrolo[3,4-c]pyridine, dihydrochloride (2.52 g, 13.06 mmol) was dissolved in 30 ml dimethylformamide with triisopropylethylamine (6.84 ml, 39.2 mmol) and added to the carbamate mixture via syringe. After stirring the mixture overnight and removing most of the solvent under vacuum, water was added; and the resulting suspension was stirred for 30 minutes and filtered to give a solid which was washed with water. Flash chromatography of the dried solid gave the title compound.
Example 153 IB
6-(2,3-dmydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylic acid The title compound was prepared as described in Example IB, substituting methyl 6- (2,3-dihydro-lH-pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylate for methyl 4-(isoindoline-2-carboxamido)benzoate.
Example 1531C
N-(6-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}pyridazin-3-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting (2S)- tetrahydrofuran-2-ylmethamine for 3-phenylpropan-l -amine and 6-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.09 (s, 1H), 8.81 (t, 7 = 6.1 Hz, 1H), 8.62 (s, 1H), 8.51 (d, 7 = 5.0 Hz, 1H), 8.31 (d, 7 = 9.3 Hz, 1H), 8.12 (d, 7 = 9.3 Hz, 1H), 7.44 (d, 7 = 5.1 Hz, 1H), 5.05 - 4.76 (m, 4H), 4.04 (p, 7 = 6.2 Hz, 1H), 3.85 - 3.74 (m, 1H), 3.70 - 3.59 (m, 1H), 3.45 - 3.31 (m, 2H), 1.99 - 1.72 (m, 3H), 1.69 - 1.54 (m, 1H); MS (ESI(+)) m/e 369 (M+H)+. Example 1542
N-(6-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}pyridazin-3-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting (2R)- tetrahydrofuran-2-ylmethamine for 3-phenylpropan-l -amine and 6-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.09 (bs, IH), 8.81 (t, 7 = 6.1 Hz, IH), 8.61 (s, IH), 8.51 (d, 7 = 5.0 Hz, IH), 8.31 (d, 7 = 9.3 Hz, IH), 8.12 (d, 7 = 9.3 Hz, IH), 7.44 (d, 7 = 5.1 Hz, IH), 5.05 - 4.76 (m, 4H), 4.04 (p, 7 = 6.2 Hz, IH), 3.85 - 3.74 (m, IH), 3.70 - 3.59 (m, IH), 3.35 (d, 7 = 25.7 Hz, 2H), 1.99 - 1.72 (m, 3H), 1.69 - 1.54 (m, IH); MS (ESI(+)) m/e 369 (M+H)+.
Example 1543
N- {6- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting tetrahydro-2H-pyran-4-ylmethamine for 3-phenylpropan-l -amine and 6-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.06 (s, IH), 9.00 (t, 7 = 6.2 Hz, IH), 8.62 (s, IH), 8.51 (d, 7 = 5.0 Hz, IH), 8.29 (d, 7 = 9.3 Hz, IH), 8.11 (d, 7 = 9.3 Hz, IH), 7.44 (d, 7 = 5.1 Hz, IH), 4.96 - 4.89 (m, 4H), 3.89 - 3.79 (m, 2H), 3.22 (d, 7 = 2.6 Hz, 3H), 1.96 - 1.75 (m, IH), 1.64 - 1.53 (m, 2H), 1.31 - 1.10 (m, 2H); MS (ESI(+)) m/e 383 (M+H)+.
Example 1544
N- { 6- [(cyclopentylmethyl)carbamoyl]pyridazin-3 -yl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting cyclopentylmethamine for 3-phenylpropan-l -amine and 6-(2,3-dihydro-lH-pyrrolo[3,4- c]pyridine-2-carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.03 (bs, IH), 8.95 (t, 7 = 6.1 Hz, IH), 8.62 (s, IH), 8.51 (d, 7 = 5.0 Hz, IH), 8.29 (d, 7 = 9.3 Hz, IH), 8.11 (d, 7 = 9.3 Hz, IH), 7.44 (d, 7 = 5.1 Hz, IH), 4.99 - 4.75 (m, 4H), 3.28 - 3.20 (m, 2H), 2.31 - 2.13 (m, IH), 1.75 - 1.38 (m, 6H), 1.39 - 1.18 (m, 2H); MS (ESI(+)) m/e 367 (M+H)+.
Example 1545
N- { 6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting tetrahydrofuran-3-ylmethamine for 3-phenylpropan-l -amine and 6-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.05 (s, 1H), 9.13 (t, J = 6.1 Hz, 1H), 8.62 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 8.30 (d, J = 9.3 Hz, 1H), 8.12 (d, J = 9.3 Hz, 1H), 7.44 (d, J = 5.1 Hz, 1H), 5.05 - 4.76 (m, 4H), 3.80 - 3.57 (m, 4H), 3.48 (dd, J = 12.1, 6.8 Hz, 1H), 3.37 - 3.31 (m, 1H), 2.62 - 2.52 (m, 1H), 2.01 - 1.80 (m, 1H), 1.71 - 1.56 (m, 1H); MS (ESI(+)) m/e 369 (M+H)+.
Example 1546
N- { 6- [(bicyclo [2.2.1 ]hept-2-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C, substituting bicyclo[2.2.1]hept-2-ylmethamine for 3-phenylpropan-l -amine and 6-(2,3-dihydro-lH- pyrrolo[3,4-c]pyridine-2-carboxamido)pyridazine-3-carboxylic acid for 4-(isoindoline-2- carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 10.05 (bs, 1H), 8.92 (d, J = 42.7 Hz, 1H), 8.61 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 8.29 (d, J = 9.3 Hz, 1H), 8.10 (d, J = 9.3 Hz, 1H), 7.47 - 7.41 (m, 1H), 5.07 - 4.74 (m, 4H), 3.23 - 2.84 (m, 2H), 2.30 - 2.02 (m, 3H), 1.86
- 1.57 (m, 2H), 1.58 - 0.99 (m, 6H); MS (ESI(+)) m/e 393 (M+H)+.
Example 1547
N-(4-{ trans-4-[(2-methylpropanoyl)amino]cyclohexyl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 : 1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and isobutyric acid for 4-(isoindoline-2- carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-(4-{trans-4- [(2-methylpropanoyl)arnino]cyclohexyl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.32 (s, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.48 - 7.40 (m, 3H), 7.17 - 7.09 (m, 2H), 4.82 - 4.76 (m, 4H), 3.65 - 3.47 (m, 1H), 2.41 - 2.23 (m, 2H), 1.93 - 1.69 (m, 4H), 1.62 - 1.38 (m, 2H), 1.39
- 1.12 (m, 2H), 0.99 (d, J = 6.8 Hz, 6H); MS (ESI(+)) m/e 407 (M+H)+.
Example 1548
N-(4-{cis-4-[(2-methylpropanoyl)arnino]cyclohexyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 : 1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and isobutyric acid for 4-(isoindoline-2- carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-(4-{cis-4- [(2-methylpropanoyl)arnino]cyclohexyl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.33 (s, 1H), 7.68 - 7.61 (m, 1H), 7.49 - 7.40 (m, 3H), 7.21 - 7.14 (m, 2H), 4.83 - 4.76 (m, 4H), 3.98 - 3.90 (m, 1H), 1.97 - 1.49 (m, 9H), 1.04 - 0.97 (m, 6H); MS (ESI(+)) m/e 407 (M+H)+.
Example 1549
N-(4-{cis-4-[(cyclohexylcarbonyl)amino]cyclohexyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 :1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and cyclohexanecarboxylic acid for 4-(isoindoline- 2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-(4-{cis-4- [(cyclohexylcarbonyl)amino]cyclohexyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.61 (s, 1H), 8.50 (d, 7 = 5.0 Hz, 1H), 8.33 (s, 1H), 7.66 - 7.59 (m, 1H), 7.47 (s, 1H), 7.47 - 7.40 (m, 2H), 7.21 - 7.14 (m, 2H), 4.83 - 4.76 (m, 4H), 3.98 - 3.90 (m, 1H), 2.45 (s, 1H), 2.31 - 2.19 (m, 1H), 1.89 - 1.46 (m, 12H), 1.46 - 1.05 (m, 6H); MS (ESI(+)) m/e 447 (M+H)+.
Example 1550
N-(4- { trans-4-[(cyclohexylcarbonyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 :1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and cyclohexanecarboxylic acid for 4-(isoindoline- 2-carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-(4-{trans- 4-[(cyclohexylcarbonyl)amino]cyclohexyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine -2- carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.49 (d, 7 = 5.0 Hz, 1H), 8.32 (s, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.47 - 7.40 (m, 3H), 7.16 - 7.09 (m, 2H), 4.82 - 4.75 (m, 4H), 3.62 - 3.42 (m, 1H), 2.42 - 2.33 (m, 1H), 2.12 - 1.99 (m, 1H), 1.87 - 1.61 (m, 8H), 1.55 - 1.37 (m, 3H), 1.38 - 1.08 (m, 7H); MS (ESI(+)) m/e 447 (M+H)+.
Example 1551
N-(4- { trans-4-[(cyclopropylacetyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 :1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and 2-cyclopropylacetic acid for 4-(isoindoline-2- carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-(4-{trans-4- [(cyclopropylacetyl)amino]cyclohexyljphenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.32 (s, 1H), 7.59 (d, 7 = 7.8 Hz, 1H), 7.48 - 7.40 (m, 3H), 7.11 (s, 2H), 4.82 - 4.76 (m, 4H), 3.66 - 3.50 (m, 1H), 2.40 (t, 7 = 10.1 Hz, 1H), 1.94 (t, 7 = 11.8 Hz, 1H), 1.83 (dd, 7 = 23.4, 12.2 Hz, 4H), 1.61 - 1.39 (m, 2H), 1.40 - 1.18 (m, 3H), 1.04 - 0.83 (m, 1H), 0.46 - 0.33 (m, 2H), 0.18 - 0.07 (m, 2H); MS (ESI(+)) m/e 419 (M+H)+.
Example 1552
N-(4-{cis-4-[(cyclopropylacetyl)amino]cyclohexyl}phenyl)-l,3-dmydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide
The title compound was prepared as described in Example 1C as a 1 :1 cis/trans mixture, substituting N-(4-(4-aminocyclohexyl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)- carboxamide for 3-phenylpropan-l -amine and 2-cyclopropylacetic acid for 4-(isoindoline-2- carboxamido)benzoic acid. HPLC separation of the cis/trans isomers provided N-(4-{cis-4- [(cyclopropylacetyl)amino]cyclohexyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide. ¾ NMR (300 MHz, DMSO-d6) δ 8.61 (s, 1H), 8.50 (d, J = 5.0 Hz, 1H), 8.33 (s, 1H), 7.67 - 7.60 (m, 1H), 7.49 - 7.40 (m, 3H), 7.21 - 7.13 (m, 2H), 4.83 - 4.76 (m, 4H), 4.02 - 3.92 (m, 1H), 2.06 (d, J = 7.0 Hz, 2H), 1.84 - 1.65 (m, 4H), 1.65 - 1.47 (m, 4H), 1.25 - 0.90 (m, 1H), 0.47 - 0.34 (m, 2H), 0.23 - 0.11 (m, 2H); MS (ESI(+)) m/e 419 (M+H)+.
Example 1553
N-(4- {4- [(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yljphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide
Example 1553 A
tert-butyl 4-(4-nitrophenyl)cyclohex-3-enylcarbamate The title was prepared as in Example 1018B, substituting 4,4,5,5-tetramethyl-2-(4- nitrophenyl)-l,3,2-dioxaborolane for N-(4-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)-lH-pyrrolo[3,4-c]pyridine-2(3H)-carboxamide.
Example 1553B
tert-butyl 4-(4-aminophenyl)cyclohex-3-enylcarbamate tert-Butyl 4-(4-nitrophenyl)cyclohex-3-enylcarbamate (2.55 g, 8.01 mmol) was suspended in ethanol (30ml) followed by addition of sodium sulfide, nonahydrate (10.37 ml, 80 mmol) dissolved in water (30ml). The mixture was heated to 80°C for 1.5 h and extracted with dichloromethane; the organic layers were combined, dried over magnesium sulfate, filtered and concentrated to give the title compound.
Example 1553C
tert-butyl 4-(4-(isoindoline-2-carboxamido)phenyl)cyclohex-3-enylcarbamate The title compound was prepared as described in Example 272B, substituting tert- butyl 4-(4-aminophenyl)cyclohex-3-enylcarbamate for 4-amino-N-propylbenzamide and isoindoline for methyl isoindoline-5-carboxylate hydrochloride.
Example 1553D
N-(4-(4-aminocyclohex- 1 -enyl)phenyl)isoindoline-2-carboxamide The title compound was prepared as described in Example 2D, substituting tert-butyl 4-(4-(isoindoline-2-carboxamido)phenyl)cyclohex-3-enylcarbamate for tert-butyl 4-((4-(5- fluoroisoindoline-2-carboxamido)benzamido)methyl)benzylcarbamate.
Example 1553E
N-(4- {4- [(2-methylpropanoyl)amino]cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and isobutyric acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO- d6) δ 8.36 (s, 1H), 7.70 (d, 7 = 7.6 Hz, 1H), 7.54 (d, 7 = 2.1 Hz, 2H), 7.46 - 7.23 (m, 6H), 6.06 - 5.96 (m, 1H), 4.76 (s, 4H), 3.85 - 3.75 (m, 1H), 2.43 - 2.26 (m, 3H), 2.11 - 1.96 (m, 1H), 1.95 - 1.75 (m, 1H), 1.69 - 1.48 (m, 1H), 1.10 - 0.82 (m, 6H); MS (ESI(+)) m/e 404 (M+H)+.
Example 1554
N- [4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3 -dihydro- 2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and - (2R)-tetrahydrofuran-2-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.61 (dt, 7 = 9.2, 4.6 Hz, 1H), 7.58 - 7.45 (m, 2H), 7.49 - 7.23 (m, 6H), 6.02 (bs, 1H), 4.77 (s, 4H), 4.25 - 4.16 (m, 1H), 3.97 - 3.66 (m, 3H), 2.42 - 2.24 (m, 1H), 2.26 - 1.98 (m, 3H), 1.98 - 1.53 (m, 6H); MS (ESI(+)) m/e 432 (M+H)+.
Example 1555
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3-dihydro- 2H-isoindole-2-carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and - (2S)-tetrahydrofuran-2-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.37 (s, 1H), 7.63 (dd, 7 = 8.2, 3.5 Hz, 1H), 7.57 - 7.50 (m, 2H), 7.49 - 7.23 (m, 6H), 6.04 - 5.96 (m, 1H), 4.76 (s, 4H), 4.25 - 4.16 (m, 1H), 3.96 - 3.67 (m, 4H), 2.38 - 2.29 (m, 1H), 2.27 - 1.99 (m, 3H), 1.97 - 1.56 (m, 5H); MS (ESI(+)) m/e 432 (M+H)+.
Example 1556
N-(4- { 4-[(cyclopentylacetyl)amino]cyclohex-l -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example 1C, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and cyclopentylacetic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.34 (s, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.57 - 7.49 (m, 2H), 7.49 - 7.23 (m, 6H),
6.01 (bs, 1H), 4.76 (s, 4H), 3.90 - 3.74 (m, 1H), 2.49 - 2.25 (m, 2H), 2.20 - 1.99 (m, 3H), 1.94 - 1.82 (m, 1H), 1.68 (tdd, 7 = 9.4, 8.9, 4.4 Hz, 2H), 1.64 - 1.42 (m, 7H), 1.31 - 1.01 (m, 2H); MS (ESI(+)) m/e 444 (M+H)+.
Example 1557
N-(4- {4- [(cyclopropylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide
The title compound was prepared as described in Example IC, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and cyclopropylacetic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.66 - 7.47 (m, 2H), 7.47 - 7.24 (m, 6H),
6.02 (bs, 1H), 4.76 (s, 4H), 3.88 - 3.78 (m, 1H), 2.49 - 2.26 (m, 3H), 2.12 - 1.82 (m, 4H), 1.72 - 1.50 (m, 1H), 1.13 - 0.88 (m, 1H), 0.52 - 0.33 (m, 2H), 0.18 - 0.01 (m, 2H); MS (ESI(+)) m/e 416 (M+H)+.
Example 1558
N-(4- { 4-[(2-hydroxy-2-methylpropanoyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide
The title compound was prepared as described in Example IC, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and 2- hydroxy-2-methylpropanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.52 (t, J = 8.6 Hz, 2H), 7.46 - 7.39 (m, 1H), 7.35 (tdd, J = 8.8, 7.1, 3.7 Hz, 6H), 6.07 - 5.96 (m, 1H), 5.40 (s, 1H), 4.77 (s, 4H), 3.92 - 3.76 (m, 1H), 2.46 (s, 1H), 2.39 - 2.25 (m, 1H), 2.24 - 2.09 (m, 2H), 1.93 - 1.78 (m, 1H), 1.70 (dt, J = 12.4, 7.7 Hz, 1H), 1.25 (s, 6H); MS (ESI(+)) m/e 420 (M+H)+.
Example 1559
N-(4- { 4- [(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide
The title compound was prepared as described in Example IC, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and tetrahydro-2H-pyran-4-carboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.57 - 7.49 (m, 2H), 7.46 - 7.23 (m, 6H), 6.02 (bs, 1H), 4.76 (s, 4H), 3.91 - 3.75 (m, 4H), 3.31 - 3.17 (m, 2H), 2.43 - 2.26 (m, 2H), 2.12 - 1.97 (m, 1H), 1.93 - 1.81 (m, 1H), 1.71 - 1.48 (m, 6H); MS (ESI(+)) m/e 446 (M+H)+. Example 1560
N-(4- { 4- [(cyclohexylcarbonyl)amino] cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide
The tide compound was prepared as described in Example 1C, substituting N-(4-(4- aminocyclohex-l-enyl)phenyl)isoindoline-2-carboxarnide for 3-phenylpropan-l -amine and cyclohexanecarboxylic acid for 4-(isoindoline-2-carboxamido)benzoic acid. ¾ NMR (300 MHz, DMSO-d6) δ 8.35 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.57 - 7.49 (m, 2H), 7.47 - 7.23 (m, 6H), 6.01 (bs, 1H), 4.76 (s, 4H), 3.84 - 3.54 (m, 1H), 2.49 - 2.24 (m, 2H), 2.20 - 1.93 (m, 2H), 1.91 - 1.77 (m, 1H), 1.78 - 1.48 (m, 6H), 1.47 - 1.06 (m, 6H); MS (ESI(+)) m/e 444 (M+H)+.

Claims

WHAT IS CLAIMED IS: acceptable salts thereof
Figure imgf000917_0001
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2,
NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein each R2 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R4, OR4, SR4, S(0)R4, S02R4, C(0)R4, CO(0)R4, OC(0)R4,
OC(0)OR4, NHC(0)R4, NR4C(0)R4, NHS(0)2R4, NR4S(0)2R4, NHC(0)OR4, NR4C(0)OR4, NHC(0)NH2, NHC(0)NHR4, NHC(0)N(R4)2, NR4C(0)NHR4, NR4C(0)N(R4)2, C(0)NH2, C(0)NHR4, C(0)N(R4)2, C(0)NHOH, C(0)NHOR4, C(0)NHS02R4, C(0)NR4S02R4, S02NH2, S02NHR4, S02N(R4)2, C(0)H, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R2 phenyl is optionally substituted at the para position with one independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5, NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, CHNOR5, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, Br or I; wherein each R2 phenyl is optionally additionally substituted with one F; wherein each R2 heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R5, OR5, SR5, S(0)R5, S02R5, C(0)R5, CO(0)R5, OC(0)R5, OC(0)OR5, NH2, NHR5, N(R5)2, NHC(0)R5, NR5C(0)R5, NHS(0)2R5, NR5S(0)2R5, NHC(0)OR5, NR5C(0)OR5,
NHC(0)NH2, NHC(0)NHR5, NHC(0)N(R5)2, NR5C(0)NHR5, NR5C(0)N(R5)2, C(0)NH2, C(0)NHR5, C(0)N(R5)2, C(0)NHOH, C(0)NHOR5, C(0)NHS02R5, C(0)NR5S02R5, S02NH2, S02NHR5, S02N(R5)2, C(0)H, C(0)OH, OH, CN, N3, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH,
C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R4, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl; wherein each R4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 7 , OR 7 , SR 7 , S(0)R 7 , S02R 7 , C(0)R7, OC(0)R7, OC(0)OR7, NH2, NHR7, NHC(0)R7, NR7C(0)R7, NHS(0)2R7,
NR7S(0)2R7, NHC(0)OR7, NR7C(0)OR7, NHC(0)NH2, NHC(0)NHR7, NHC(0)N(R7)2, NR7C(0)NHR7, NR7C(0)N(R7)2, C(0)NH2, C(0)NHR7, C(0)N(R7)2, C(0)NHOH,
C(0)NHOR7, C(0)NHS02R7, C(0)NR7S02R7, S02NH2, S02NHR7, S02N(R7)2, C(0)H, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R4 aryl and heterocycyl is optionally substituted with one, two, three or four independently selected R8, OR8, SR8, S(0)R8, S02R8, C(0)R8, CO(0)R8, OC(0)R8, OC(0)OR8, NH2, NHR8, NHC(0)R8, NR8C(0)R8, NHS(0)2R8, NR8S(0)2R8, NHC(0)OR8, NR8C(0)OR8, NHC(0)NH2,
NHC(0)NHR8, NHC(0)N(R8)2, NR8C(0)NHR8, NR8C(0)N(R8)2, C(0)NH2, C(0)NHR8, C(0)N(R8)2, C(0)NHOH, C(0)NHOR8, C(0)NHS02R8, C(0)NR8S02R8, S02NH2,
S02NHR8, S02N(R8)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2,
NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R7, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R11, OR11, SR11, S(0)Rn, S02Rn, NHR11, N(Rn)2, C(0)Rn, C(0)NH2, C(0)NHRn, C(0)N(Rn)2,
NHC(0)Rn, NRnC(0)Rn, NHS02Rn, NHC(0)ORn, S02NH2, S02NHRn, S02N(Rn)2, NHC(0)NH2, NHC(0)NHRn, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2,
NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R11, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R12, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R5, R6, R7, R8, R9, R10, R11, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R , NR13C(0)R , NHS(0)2R , NR13S(0)2R , NHC(0)OR , NR13C(0)OR , NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F,
CI, Br, or I; wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy; R , at each occurrence, is independently selected alkyl; wherein the R alkyl is optionally substituted with one, two, three or four alkoxy;
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when X1, X2, and X3 are CH and R2 is phenyl; R5 is not methyl; with the proviso that when X1, X2, and X3 are CH, and R2 is phenyl substituted with OR5; R5 is not methyl;
with the proviso that when R2 is unsubstituted alkyl or optionally substituted alkyl; R2 is C4-C6-alkyl;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
2. A compound having Formula (Vc), or pharmaceutically acceptable salts thereof
Figure imgf000921_0001
(Vc);
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R5, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R9, OR9, SR9, S(0)R9, S02R9, C(0)R9, CO(0)R9, OC(0)R9, OC(0)OR9, NH2, NHR9, N(R9)2, NHC(0)R9, NR9C(0)R9, NHS(0)2R9, NR9S(0)2R9, NHC(0)OR9, NR9C(0)OR9, NHC(0)NH2,
NHC(0)NHR9, NHC(0)N(R9)2, NR9C(0)NHR9, NR9C(0)N(R9)2, C(0)NH2, C(0)NHR9, C(0)N(R9)2, C(0)NHOH, C(0)NHOR9, C(0)NHS02R9, C(0)NR9S02R9, S02NH2, S02NHR9, S02N(R9)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R9, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R5, R6, R9, and R10 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R , S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3,
OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl, wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy; with the proviso that when R is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
3. A compound having Formula (VIIc), or pharmaceutically acceptable salts
Figure imgf000924_0001
(VIIc);
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
1 is N; X2 is CR1; and X3 is N;
Figure imgf000924_0002
a single or double bond;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2, NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6, NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2, NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
wherein the cyclic moieties represented by R3, R6, andR10 are optionally substituted with one, two, three, four, five, or six independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2,
C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR13, C(0)NHS02R13, C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydro furanyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR13C(0)R , NHS(0)2R , NR13S(0)2R , NHC(0)OR , NR13C(0)OR , NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2, C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I;
R15, at each occurrence, is independently selected alkyl, wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; and
R16, at each occurrence, is independently selected alkyl, wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
4. A compound having Formula (VIIIc), or pharmaceutically acceptable salts thereof
Figure imgf000926_0001
(VIIIc);
wherein
X1, X2, and X3 are CH; or
X1 and X3 are CH; and X2 is N; or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N;
R1 is R3, OR3, SR3, S(0)R3, S02R3, C(0)R3, C(0)OR3, OC(0)R3, NHR3, N(R3)2, C(0)NH2, C(0)NHR3, C(0)N(R3)2, NHC(0)R3, NR3C(0)R3, NHC(0)OR3, NR3C(0)OR3, S02NH2, S02NHR3, S02N(R3)2, NHS02R3, NR3S02R3, NHS02NHR3, NHS02N(R3)2,
NR3S02NHR3, NR3S02N(R3)2, C(0)NHS02R3, NHS02NHR3, F, CI, Br, I, CN, NH2, N02, N3, OH, C(0)H, CF3, C(0)OH, or C(0)NH2;
R3, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R6, OR6, SR6, S(0)R6, S02R6, C(0)R6, CO(0)R6, OC(0)R6, OC(0)OR6, NH2, NHR6, N(R6)2, NHC(0)R6, NR6C(0)R6, NHS(0)2R6,
NR6S(0)2R6, NHC(0)OR6, NR6C(0)OR6, NHC(0)NH2, NHC(0)NHR6, NHC(0)N(R6)2, NR6C(0)NHR6, NR6C(0)N(R6)2, C(0)NH2, C(0)NHR6, C(0)N(R6)2, C(0)NHOH, C(0)NHOR6, C(0)NHS02R6, C(0)NR6S02R6, S02NH2, S02NHR6, S02N(R6)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R6, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R10, OR10, SR10, S(0)R10, S02R10, NHR10, N(R10)2, C(0)R10, C(0)NH2, C(0)NHR10, C(O)N(R10)2,
NHC(0)R10, NR10C(O)R10, NHS02R10, NHC(0)OR10, S02NH2, S02NHR10, SO2N(R10)2,
NHC(0)NH2, NHC(0)NHR10, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R8, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R12, OR12, SR12, S(0)R12, S02R12, NHR12, N(R12)2, C(0)R12, C(0)NH2, C(0)NHR12, C(0)N(R12)2,
NHC(0)R12, NR12C(0)R12, NHS02R12, NHC(0)OR12, S02NH2, S02NHR12, S02N(R12)2, NHC(0)NH2, NHC(0)NHR12, OH, (O), C(0)OH, N3, CN, NH2, CF3, CF2CF3, F, CI, Br or I;
R10, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
R12, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
wherein the cyclic moieties represented by R3, R6, R8, R10, and R12 are optionally substituted with one, two, three, four, five, or six independently selected R13, OR13, SR13, S(0)R13, S02R13, C(0)R13, CO(0)R13, OC(0)R13, OC(0)OR13, NH2, NHR13, N(R13)2, NHC(0)R13, NR13C(0)R13, NHS(0)2R13, NR13S(0)2R13, NHC(0)OR13, NR13C(0)OR13, NHC(0)NH2, NHC(0)NHR13, NHC(0)N(R13)2, NR13C(0)NHR13, NR13C(0)N(R13)2, C(0)NH2, C(0)NHR13, C(0)N(R13)2, C(0)NHOH, C(0)NHOR , C(0)NHS02R ,
C(0)NR13S02R13, S02NH2, S02NHR13, S02N(R13)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, SCF3, F, CI, Br or I;
R13, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkenyl; wherein each R13 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R14, OR14, SR14, S(0)R14, S02R14, C(0)R14, OC(0)R14, OC(0)OR14, NH2, NHR14, N(R14)2, NHC(0)R14, NR14C(0)R14, NHS(0)2R14, NR14S(0)2R14, NHC(0)OR14, NR14C(0)OR14, NHC(0)NH2, NHC(0)NHR14, NHC(0)N(R14)2, NR14C(0)NHR14, NR14C(0)N(R14)2, C(0)NH2,
C(0)NHR14, C(0)N(R14)2, C(0)NHOH, C(0)NHOR14, C(0)NHS02R14, C(0)NR14S02R14, S02NH2, S02NHR14, S02N(R14)2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R13 aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2- onyl, l,l-dioxidotetrahydrothien-3-yl, l,l-dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R15, OR15, SR15, S(0)R15, S02R15, C(0)R15, CO(0)R15, OC(0)R15, OC(0)OR15, NH2, NHR15, N(R15)2, NHC(0)R15, NR15C(0)R15, NHS(0)2R15, NR15S(0)2R15, NHC(0)OR15, NR15C(0)OR15, NHC(0)NH2, NHC(0)NHR15, NHC(0)N(R15)2, NR15C(0)NHR15, NR15C(0)N(R15)2, C(0)NH2,
C(0)NHR15, C(0)N(R15)2, C(0)NHOH, C(0)NHOR15, C(0)NHS02R15, C(0)NR15S02R15, S02NH2, S02NHR15, S02N(R15)2, C(0)H, C(0)OH, OH, CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I;
R14, at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH2, S02NH2, C(0)H, C(0)OH, OH, (O), CN, N3, N02, CF3, CF2CF3, OCF3, OCF2CF3, F, CI, Br or I; wherein each R14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R16, OR16, OH, F, CI, Br, or I; wherein the R16 alkyl is optionally substituted with one, two, three or four alkoxy;
R15, at each occurrence, is independently selected alkyl; wherein the R15 alkyl is optionally substituted with one, two, three or four alkoxy; R , at each occurrence, is independently selected alkyl, wherein the R alkyl is optionally substituted with one, two, three or four alkoxy;
with the proviso that when R13 is piperidinyl, it is substituted piperidinyl; and with the proviso that when R13 is pyrrolinyl, at least one of X1, X2, and X3 is N.
5. The compound of claim 1, claim 2, claim 3, or claim 4, or pharmaceutically acceptable salts thereof; wherein
X1, X2, and X3 are CH, or
X1 and X3 are CH; and X2 is CR1; or
X2 and X3 are CH; and X1 is CR1; or
X1 is CH; and X2 and X3 are CR1.
6. The compound of claim 1, claim 2, claim 3, or claim 4, or pharmaceutically acceptable salts thereof; wherein
X1 and X3 are CH; and X2 is N; or
X2 is CH; and X1 and X3 are N; or
X2 and X3 are CH; and X1 is N; or
X1 is CH; X2 is N; and X3 is CR1; or
X1 is CR1; X2 is N; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is CH; or
X1 is N; X2 is CR1; and X3 is N.
7. The compound of claim 1, claim 2, claim 3, or claim 4, or pharmaceutically acceptable salts thereof; wherein
X1 and X3 are CH; and X2 is N.
8. The compound of claim 1, or pharmaceutically acceptable salts thereof; wherein
R2 is phenyl which is substituted at the para position with R5; and
R5 is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7,8- tetrahydrophthalazin- 1 (2H)-onyl, 5-fluorophthalazin-l (2H)-onyl, (Z)-3H- benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2- d][l,2,4]triazin-l(2H)-one, or isoindolin-l-onyl. 9. The compound of claim 1, selected from the group consisting of:
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(aminomethyl)benzyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(furo[3,2-c]pyridin-4-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(pyridin-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] -5-fluoro- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methyl-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(thieno[3,2-c]pyridin-4-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(2,3-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4- [(3 -phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [4-(pyridazin-3-yl)piperazin-l-yl]carbonyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2,3-dihydro- 1 ,4-benzodioxin-5-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(3-methylbutyl)-lH-pyrazol-4-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3-methylbutyl)carbamo yl]phenyl}-l, 3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(2-oxopyrrolidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-methyl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-{4-[(4-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-fluoro-5-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [4-(pyrazin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
5-methoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [4-(pyrimidin-2 -yl)piperazin- 1 -yl] carbonyl } phenyl) -1,3 -dihydro-2H-isoindole-
2-carboxamide;
5-nitro-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; 5-methyl-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(4-fluorophenyl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyrimidin-2-yl)piperazin- 1 -yl]carbonyl}phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(2-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(3-methoxyphenyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(4-acetylphenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(2,3-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-thienylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-2-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4-chloro-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4-phenylpiperazin-l-yl)carbonyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(6-aminohexyl)carbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide;
4- chloro-N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-thienyl)ethyl]carbamoyl jphenyl)- 1 , 3-dihydro-2H-isoindole-2- carboxamide;
5- methoxy-N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 ,3-benzodioxol-5-ylmethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-3-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridazin-3-yl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(3-fluorophenyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(pyridin-2-yl)piperazin- 1 -yljcarbonyl }phenyl)-5-(trifluoromethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3-butoxypropyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide; N-(4-{ [2-(3,4-dihydroxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-propoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-furylmethyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(2-cyanophenyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(3-hydroxy-2-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)carbamoyl]phenyl}-5-(trifluoromethyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methyl-lH-indazol-5-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-5-(trifluoromethyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(2,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
methyl 5-({4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl} amino)- 1H- indazole-3-carboxylate;
N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(5-chloropyridin-2-yl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-indol-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethyl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole -2- carboxamide;
N-{4-[(3,5-dimethoxyphenyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro- 1 ,4-benzodioxin-6-ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(2-fluorobenzoyl)piperazin- 1 -yl]carbonyl} phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(5-methoxy- lH-indol-3-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(2-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-propoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(pyridin-4-yl)piperazin- 1 -yl] carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- [4 -( { 2- [4-(dimethylamino)phenyl] ethyl } carbamoyl)phenyl] -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(4-{ [3-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(lR)-3-hydroxy- 1 -phenylpropyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-fluoro-4-methoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(isobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(l ,3-benzodioxol-5-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(2-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-isopropoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
4- chloro-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxamide; N- { 4- [(2-phenoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-hydroxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ l-[(3S)-tetrahydrofuran-3-yl]-lH-pyrazol-4-yljcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5- methyl-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(2-phenylethyl)carbamoyl]phenylj-1 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(methylthio)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-ethoxyethyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(2-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 4-[(trifluoromethyl)thio]benzyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-fluorophenyl)pyrrolidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(lH-imidazol-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(hydroxymethyl)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-benzodioxol-5-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -isopropyl- lH-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[methyl(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(thiomorpholin-4-ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(2-furoyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzylpiperidin-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(5-acetamido-2-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(3,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ 2-[3-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-( 1 H-imidazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1R)- 1 -(3-cyanophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [benzyl(2-hydroxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-cyanophenyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(4-chlorophenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(pyridin-2-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyanomethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(cyclohexylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[butyl(methyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [4-(dimemylamino)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,4-dihydroisoquinolin-2(lH)-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-dihydro-2H-isoindol-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro-lH-indol-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(phenylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(diemylarrdno)emyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-hydroxy-2-phenylethyl)(methyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-aminophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
tert-butyl (1 - { 4-[( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl }piperidin-4- yl)carbamate;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 4- [3-chloro-5 -(trifluoromethyl)pyridin-2-yl]piperazin- 1 -yl } carbonyl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(cyclohexylmethyl)piperazin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4-{ [l-(3-chlorobenzyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(diethylcarbamoyl)piperidin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(piperidin-l -yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-hydroxyethyl)piperazin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-hydroxy-6-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(dimethylarnino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-hydroxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5,6-dihydro[l,2,4]triazolo[4,3-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(5-fluoropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopropylmethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3,4,9-tetrahydro-2H-beta-carbolin-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tert-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-({ 4-[4-(trifluoromethyl)phenyl]piperazin- 1 -yl}carbonyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{ 4-[(3,3-difluoropyrrolidin- 1 -yl)carbonyl]phenyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(3S)-l-benzylpyrrolidin-3-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(4-carbamoylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopropylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-[4-(methylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(dimethylamino)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(pentan-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(pentan-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[( 1 ,3-dioxolan-2-ylmethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(4-fluorophenyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l -phenyl- lH-pyrazol-4-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ 2-[4-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methoxyethyl)(propyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(sec-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [3-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[bis(2-ethoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [butyl(ethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [isobutyl(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [(3-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-carbamoylphenyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)-2-(trifluoromethyl)pyrrolidin- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(lR)-2-hydroxy- 1 -phenylethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-methylpyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[ethyl(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,6-dimethylmorpholin-4-yl)carbonyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)- 1 -hydroxybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2,5-dimethylpyrrolidin- 1 -yl)carbonyl]phenyl }- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(prop-2-yn- 1 -ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [isopropyl(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[isopropyl(propyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-cyanoethyl)(cyclopropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[ethyl(isopropyl)carbamoyl]phenyl}-13-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-fluoropyrrolidin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl}-N-isopropyl-beta- alanine;
N-{4-[methyl(propyl)carbamoyl]phenyl}-1 -dihydro-2H-isoindole-2-carboxamide; 5,6-dimethoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(4-chlorophenoxy)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethoxy)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-phenyl- 1 ,3-thiazol-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
methyl 2- { [4-(propylcarbamoyl)phenyl] carbamoyl } isoindoline-5-carboxylate;
2-{ [4-(propylcarbamoyl)phenyl]carbamoyl}isoindoline-5-carboxylic acid;
5-amino-N- [4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-(aminomethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(2-hydroxy-2-methylpropanoyl)amino] -N- [4-(propylcarbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(N,N-dimethylglycyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide; 5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-[(methylsulfonyl)amino] -N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-[4-(propylcarbamoyl)phenyl]-13-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [4-(pyridin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(4,4,4-trifluorobutanoyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(4-phenylbutanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-methylpentanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(benzyloxy)acetyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(3-phenylpropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3-phenoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [N-(2-furoyl)glycyl] amino jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [4-(2-thienyl)butanoyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-oxo-4-phenylbutanoyl)amino]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(N-benzoylglycyl)amino]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(4-phenoxybutanoyl)amino]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(propionylamino)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(pentanoylamino)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(hexanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(heptanoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(pent-4-enoylamino)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(ethoxyacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [(2-methoxyethoxy)acetyl] amino jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyclopropylacetyl)amino]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [3-(4-methylpiperazin-l -yl)propanoyl] amino jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
methyl 2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5- carboxylate;
2-({4-[(cyclopentylacetyl)amino]phenyl}carbamoyl)isoindoline-5-carboxylic acid;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-cyclopentylethyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4- { 4-[(l ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } -3,6- dihydropyridine- 1 (2H)-carboxylate;
N-[4-(l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -methyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [( 1 E)-5-phenylpent- 1 -en- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -propyl- lH-pyrazol-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzyl- lH-pyrazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(2-hydroxyethyl)-lH-pyrazol-4-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[6-(l -propyl- lH-pyrazol-4-yl)pyridin-3-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[l -(3-methylbutyl)- lH-pyrazol-4-yl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- [4 -(5 -phenylpentyl)phenyl] -1,3 -dihydro-2H-isoindole-2 -carboxamide;
N-[2-fluoro-4-(l -propyl- lH-pyrazol-4-yl)phenyl] -1, 3-dihydro-2H-isoindole -2- carboxamide;
N- { 2-fluoro-4- [ 1 -(3-methylbutyl)- 1 H-pyrazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l-butyryl-l,2 ,6-tetrahydropyridin-4-yl)phenyl]-1 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [ 1 -(isopropylsulfonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(r-isobutyryl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(r-benzoyl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-benzoylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(isopropylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(phenylsulfonyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(benzoylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [3 -(butyrylamino)pyrrolidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperazine- 1 - carboxylate;
N-[4-(4-propionylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[4-(cyclopropylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-butyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-isobutyryl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(2-benzoyl-2,3-dihydro-lH-isoindol-5-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[2-(3-methylbutyl)-2,3-dihydro-lH-isoindol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexyloxy)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[6-(4-chlorophenoxy)hexyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(piperidin-4-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N,N'-hexane-l,6-diylbis(l,3-dihydro-2H-isoindole-2-carboxamide);
N-(4 -phenylbutyl) -1,3 -dihydro -2H-isoindole-2-carboxamide ;
ethyl 6-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]hexanoate;
N-hexyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-octyl-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [( 1 -methyl- 1 H-pyrazol-4-yl)amino] -6-oxohexyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[6-(memylamino)-6-oxohexyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N- { 6-0X0-6- [(3-phenylpropyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [(3-methylbutyl)amino] -6-oxohexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(5 - { [4-(pyridin-2-yl)piperazin- 1 -yl] carbonyl }pyridin-2-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 5-[(3-phenylpropyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{5-[(3-methylbutyl)carbamoyl]pyridin-2-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 5-[(3-phenylpropyl)carbamoyl] - 1 ,3-thiazol-2-yl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 5-[(3-methylbutyl)carbamoyl]- 1 ,3-thiazol-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(isoquinolin-4-yl)phenyl]-1 -dmydro-2H-isoindole-2-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4, 5,6,7, 8-hexahydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(8-fluoro-4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole- 2-carboxamide;
5-fluoro-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -5-(pyrrolidin- 1 -ylmethyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-(morpholin-4-ylmethyl)-N-[4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-methoxy-N- [4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- [(4-methylpiperazin- 1 -yl)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-[4-(l -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-chloro-N- [4-( 1 -oxo-1 ,2-dihydroisoquinolin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole- 2-carboxamide;
N-[4-(4-oxo-4,5-dihydro-3H-2,3-benzodiazepin-l-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]-5-(pyrrolidin-l -ylmethyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4-yl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(l -oxo- 1 ,2-dihydroisoquinolin-4-yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-[(4-methylpiperazin-l-yl)methyl]-N-[4-(l -oxo-1, 2-dihydroisoquinolin-4- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-[(dimethylamino)methyl]-N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-[(diethylamino)methyl] -N- [4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[4-oxo-8-(trifluoromethyl)-3,4-dihydrophthalazin- 1 -yl]phenyl } -5-(pyrrolidin- 1 - ylmethyl)- l,3-dihydro-2H-isoindole -2-carboxamide;
5-[(l -methylpiperidin-4-yl)oxy] -N- [4-(4-oxo-3,4-dihydrophthalazin-l -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-{ [(3R)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-{ [(3S)-3-fluoropyrrolidin-l-yl]methyl}-N-[4-(4-oxo-3,4-dihydrophthalazin-l- yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; 5-(azetidin- 1 -ylmethyl)-N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl]- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxo-l,2-dihydropyrrolo[l,2-d] [l,2,4]triazin-4-yl)phenyl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperidine- 1 - carboxylate;
N-[4-(5-propyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(piperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 5-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-2-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-butyrylpiperidin-4-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[5-(3-methylbutyl)-l,2,4-oxadiazol-3-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-benzyl-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(5-chloropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-hydroxy-4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-oxopyrrolidin- 1 -yl)benzyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(lS,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide; N-(4- { [(1 -hydroxycyclopropyl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl 4-{6-[(1 -dihydro-2H-isoindol-2-ylcarbonyl)amino]-lH-benzimidazol-2- yl}piperazine-l-carboxylate;
N-[2-(piperazin- 1 -yl)- lH-benzimidazol-6-yl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] -5-vinyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-benzoylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(tetrahydrofuran-3-yl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- d]pyrimidine-6-carboxamide;
N-(4-{ [(3-phenylpropyl)arnino]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- d]pyrimidine-6-carboxamide;
N-{4-[l-(4-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -benzyl- 1,2,3, 6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(tetrahydrofuran-3-ylmethyl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2S)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2R)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide; N- [4 -( { [( 1 S) -2-hydroxy- 1 -phenylethyl] amino } carbonyl)phenyl] -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [4-(2-methoxyethyl)piperazin-l -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-2-(2-hydroxyethyl)piperidin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-3-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-4-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N5-(2-methoxyethyl)-N2-{4-[(propylamino)carbonyl]phenyl}-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N-(4-cyanophenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(trifluoromethyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4 - { [(tetrahydrofuran-3 -ylmethyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-pyridin-2-ylpiperazin-l-yl)carbonyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
5-( 1 ,2-dihydroxyethyl)-N- { 4- [(propylamino)carbonyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-5-cyano-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(l'-butyryl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(r-isobutyryl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide; and
N-[2-(4-acetylpiperazin-l-yl)-lH-benzimidazol-5-yl]-l,3-dihydro-2H-isoindole-2- carboxamide; N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(5-oxo-D-prolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -propionyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N- { 4- [ 1 -(2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(ethoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(2-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(3-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(4-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N-{4-[l-(3-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(4-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(4-chlorobenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[3-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[4-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(3-furoyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[l -(3-thienylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(lH-pyrrol-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(2,5 -dimethyl- lH-pyrrol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,3-thiazol-4-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(lH-pyrazol-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(3,5 -dimethyl- 1 ,2-oxazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-
2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-( 1 -isonicotinoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(pyridazin-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrimidin-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide; N-(4- { 1 -[3-(piperidin- 1 -yl)propanoyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(r-benzoyl-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [6-(benzoylamino)hexyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[(benzoylamino)methyl]benzyljcarbamoyl)phenyl]-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { 4- [4-(5-oxo-L-prolyl)piperazin- 1 -yljphenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(5-oxo-D-prolyl)piperazin-l -yljphenyl }-l, 3-dihydro-2H-isoindole -2- carboxamide;
N-(4- {4-[(l -acetylpiperidin-4-yl)carbonyl]piperazin-l -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(2-acetamidobenzoyl)piperazin-l -yljphenyl} -l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[4-(methylsulfonyl)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-butyrylpiperazin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(4-isobutyrylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(2-methylbutanoyl)piperazin- 1 -yljphenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3,3,3-trifluoropropanoyl)piperazin- 1 -yljphenyl }- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(methoxyacetyl)piperazin-l -yljphenyl} -l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yljphenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[4-(tetrahydrofuran-3-ylcarbonyl)piperazin- 1 -yljphenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[4-(cyclopentylacetyl)piperazin-l -yljphenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{ 4-[4-(cyclohexylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(2-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-methoxybenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(3-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(2-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-chlorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(3-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- { 4- [4-(4-cyanobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- {4-[3-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {4-[4-(dimethylamino)benzoyl]piperazin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[4-(3,4-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(3,5-dimethoxybenzoyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 4 - [(3 ,4 -dimethoxyphenyl) acetyl] piperazin- 1 -yl } phenyl)- 1 , 3 -dihydro-2H- isoindole-2-carboxamide;
N- { 4- [4-(2-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [4-(3-furoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[4-(lH-pyrrol-2-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(lH-pyrazol-5-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(pyridin-2-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[4-(pyridin-3-ylcarbonyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-isonicotinoylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyridazin-3-ylcarbonyl)piperazin- 1 -yl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrazin-2-ylcarbonyl)piperazin- 1 -yl]phenyl } -1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(pyrimidin-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[4-(N,N-dimethyl-beta-alanyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-acetylpiperazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole -2-carboxamide; N-{ 4-[4-(2-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(4-fluorobenzoyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[4-(phenylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[4-(l,3-thiazol-4-ylcarbonyl)piperazin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-{4-[4-(morpholin-4-ylacetyl)piperazin-l-yl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-phenylbutyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-[4-(l -oxo-2, 3-dihydro-lH-isoindol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-( 1 -oxo- 1 ,2-dihydroisoquinolin-4-yl)cyclohex-3 -en- 1 -yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4-oxo-3,4-dihydrophthalazin-l-yl)cyclohex-3-en-l-yl]-5-(pyrrolidin-l- ylmethyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[l -(3-methylbutyl)- lH-pyrazol-4-yl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[l -(2-phenylethyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N5-[2-(dimethylamino)ethyl]-N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- {benzyl[3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(isobutoxycarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
5-bromo-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
methyl 4-{ [(5-cyano-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoate;
N-(4- { (E)-[(benzyloxy)imino]methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-
2H-isoindole-2-carboxamide; 5-fluoro-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-aminopyrrolidin-l-yl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-{6-[(3-methylbutyl)carbamoyl]pyridin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(3-phenylpropyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dihydro-2H-isoindole-2,5- dicarboxamide;
N-[4-({benzyl[3-(morpholin-4-yl)propyl] amino }methyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(pyridin-3-yl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -methyl- lH-pyrazol-4-yl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-methoxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N2- { 4-[(cyclopentylacetyl)amino]phenyl } -N5-(2-hydroxyethyl)- 1 ,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(aminomethyl)-N- { 4-[(cyclopentylacetyl)amino]phenyl} - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-(methylthio)butan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2S,3S)-1 -hydroxy-3-methylpentan-2-yl]carbamoyl Jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [(2S R)-13-dmydroxybutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xyhexan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-1 -hydro xypentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S,2S)-2-hydroxycyclopentyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { [( 1 S ,2R) -2-hydroxycyclopentyl] carb amoyl } phenyl) -1,3 -dihydro -2H-isoindole- 2-carboxamide;
N-(4- { [(2S)- 1 -cyclohexyl-3-hydroxypropan-2-yl] carbamoyl jphenyl)- 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ (2R)- 1 -hydroxy-3-[(4-methylbenzyl)thio]propan-2-yl }carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(IS)- 1 -(4-tert-butylphenyl)-2-hydroxyethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methoxy- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-memyl-N-[4-(propylcarbamoyl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxamide; N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-phenylethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[6-(benzoylamino)hexyl] - 1 ,3-dihydro-2H-isoindole -2-carboxamide;
N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dmydro-2H-isoindole-2-carboxamide;
N- { 4- [(cyclopentylacetyl)amino]phenyl } -5-(pyridin-4-yl)- 1 ,3 -dihydro-2H-isoindole- 2-carboxamide; 5-(hydroxymethyl)-N- { 4-[(3-methylbutyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-yl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4-phenylbutyl)-l,3-dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-[l -(3-methylbutyl)- lH-pyrazol-4-yl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 5-[(3-methylbutyl)carbamoyl]pyrazin-2-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6-acetamidohexyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(2-methoxyethoxy)acetyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { ( 1 E) -3 - [benzyl(methyl) amino]prop- 1 -en- 1 -yl } phenyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(4-phenoxypiperidin- 1 -yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(3-phenoxyazetidin-l-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [benzyl(methyl)amino] methyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(4-hydroxypiperidin-l-yl)carbonyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2 carboxamide; N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5,6-dihydroimidazo[l,5-a]pyrazin-7(8H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(3-methylbutyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1H- 1 ,2,3-triazol-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[2-(2-oxopyrrolidin-l-yl)ethyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(l-benzylpiperidin-4-yl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-phenylpropyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ l-[4-(morpholin-4-yl)benzyl]-lH-l,2,3-triazol-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-isobutyl-lH-l,2,3-triazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[l-(cyclopentylmethyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methoxypropyl)-lH-l,2,3-triazol-4-yl]phenylj-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-
2-carboxamide; N-{5-[l-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]pyridin-2-yl}-1 -dihydro-2H- isoindole-2-carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-3-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-(4- { [(2 -methoxyethoxy) acetyl] amino } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(l'-isobutyryl-l',2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(l'-benzoyl-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-3-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ r-[(2-methoxyethoxy)acetyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [4-(methylsulfonyl)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(ethoxyacetyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 6- [(cyclopentylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 6-[(2-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 6-[(3-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 6-[(4-hydroxybenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 6- [(2-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(3-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-methoxybenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(2-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 6-[(3-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-fluorobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 6- [(2-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(3-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-chlorobenzoyl)amino]hexyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; N- { 6- [(3-cyanobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 6- [(4-cyanobenzoyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(6-{ [3-(dimemylamino)benzoyl]amino jhexyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [4-(dimethylamino)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-(6-{ [3-(trifluoromethyl)benzoyl]amino jhexyl)- l,3-dihydro-2H-isoindole -2- carboxamide;
N-(6-{ [4-(trifluoromemyl)benzoyl]amino jhexyl)- l,3-dihydro-2H-isoindole -2- carboxamide;
N-(6- { [3-(trifluoromethoxy)benzoyl] amino jhexyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,3-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,4-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(2,5-dimethoxybenzoyl)amino]hexylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(phenylacetyl)amino]hexylj-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(6- { [(3-fluorophenyl)acetyl]amino jhexyl)- 1 , 3-dihydro-2H-iso indole-2- carboxamide;
5-(hydroxymethyl)-N- { 4-[(tetrahydrofuran-2-ylacetyl)amino]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(ethoxyacetyl)amino]phenyl } -5-(hydroxymethyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-(hydroxymethyl)-N-{4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]phenylj-l,3- dihydro-2H-isoindole-2-carboxamide;
5-(hydroxymethyl)-N-{4-[(morpholin-4-ylacetyl)amino]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(morpholin-4-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[6-(benzoylarrdno)hexyl]-13-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
4- fluoro-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
5- fluoro-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [(pyridin-3 -ylcarbonyl)amino]hexyl } -5-(trifluoromethyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide; 4- cyano-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5- methyl-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- { 6-[(pyridin-3-ylcarbonyl)amino]hexyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-chloro-N-{6-[(pyridin-3-ylcarbonyl)amino]hexyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{6-[(pyridin-2-ylcarbonyl)amino]hexyl}-1 -dihydro-2H-isoindole-2-carboxamide; N- { 4- [ 1 -(pyridin-2-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 1 '-[( 1, 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-2,4'- bipyridin-5-yl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ 1-[(1 -methylpyrrolidin-3-yl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide; N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(l,4-dioxan-2-ylcarbonyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ r-[(l-methylpyrrolidin-3-yl)carbonyl]-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl}- l,3-dihydro-2H-isoindole-2-carboxamide;
N- { Γ- [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-2,4'- bipyridin-5 -yl } - 1 , 3 -dihydro-2H-isoindole-2 -carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(7 -oxo-7- { [(3R)-tetrahydrofuran-3-ylmethyl]aminojheptyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 7-oxo-7-[(tetrahydro-2H-pyran-4-ylmethyl)amino]heptyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[methyl(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(azetidin- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide; N-{4-[methyl(propyl)carbamoyl]phenyl}-1 -dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(2-methoxyethyl)(methyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N- { 4- [methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[benzyl(methyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide; N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(trifluoromethyl)piperidin- 1 -yl]carbonyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3 ,4- c]pyridine-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[5-(morpholin-4-ylmethyl)- 1 ,2,4-oxadiazol-3-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{5-[(4-methylpiperazin-l-yl)methyl]-l,2,4-oxadiazol-3-yl Jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(5-{ [(3-methylbutyl)amino]methyl}-l,2,4-oxadiazol-3-yl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- {5-[(4-hydroxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl Jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-chlorobenzoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydrofuran-2-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[r-(tetrahydro-2H-pyran-4-ylcarbonyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]- l,3-dihydro-2H-isoindole-2-carboxamide; N-[l'-(l,4-dioxan-2-ylcarbonyl)-1^2^3^6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N- { Γ- [( 1 -methylpyrrolidin-3-yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3 ,4'-bipyridin-6-yl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 1 '-[( 1, 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] - 1 ',2',3',6'-tetrahydro-3,4'- bipyridin-6-yl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[r-(2-hydroxy-2-methylpropanoyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [3-(dimethylarnino)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [4-(2-aminoethyl)- lH-irnidazol- 1 -yl]carbonyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 4- [2-(2-hydroxyethoxy)ethyl]piperazin- 1 -yl } carbonyl)phenyl] - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(dimethylarnino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-methoxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide; N-[4-({ [(4S)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ [(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}carbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino } -2-oxoethyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(3- {benzyl[3-(morpholin-4-yl)propyl] amino } -3-oxopropyl)phenyl] - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2R)-butan-2-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
4- cyano-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-methyl- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5- chloro-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(6-bromo-2-oxoquinolin-l(2H)-yl)butyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[6-(3-acetylphenyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[r-(morpholin-4-ylacetyl)-r,2',3',6'-tetrahydro-2,4'-bipyridin-5-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[r-(morpholin-4-ylacetyl)-r,2',3',6'-tetrahydro-3,4'-bipyridin-6-yl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide; N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(2- { (4-fluorobenzyl)[4-(pyridin-3-yl)benzyl]amino } - 1 ,3-miazol-5-yl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2 -benzyl- l,3-thiazol-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(7 - { benzyl [3 -(morpholin-4-yl)propyl] amino } -7 -oxoheptyl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)sulfamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(cyclopentylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- { 4-[(l ,3-thiazol-5-ylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1R) -3 -hydroxy- 1 -phenylpropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(4-methylphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(l ,3-dihydroxypropan-2-yl)carbamoyl]phenylj - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3 -dihydro -2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2R)-l-hydroxy-3-methylbutan-2-yl]carbamoyljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2-(4-methylpiperazin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyljcarbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(4-hydroxybutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- {4-[(3-furylmethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide; 5-cyano-N- {4-[(tetrahydro furan-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(2-furoyl)piperazin- 1 -yl]carbonyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(tetrahydrofuran-2-ylcarbonyl)piperazin- 1 -yljcarbonyl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
5-cyano-N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-tetrahydrofuran-2-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [4-(ethylsulfonyl)piperazin- 1 -yljcarbonyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- {4-[(tetrahydro furan-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(lR)-2-hydroxy-l -phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2S)-1 -hydro xybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2,3-dihydroxypropyl)carbamoyl]phenylj - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(pyridin-2-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(l -hydroxy-4-methylpentan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(5-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyljpyridin-2-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.3]hept-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.4]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(3,9-diazaspiro[5.5]undec-3-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- {benzyl[3-(morpholin-4-yl)propyl] amino } -4-oxobutyl)phenyl] - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N-(4-phenylbutyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2- {benzyl[3-(morpholin-4-yl)propyl] amino }ethyl)phenyl]- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-acetyl-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(l -hydroxy ethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(butyrylamino)phenyl] -5-cyano- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methoxybenzyl) sulfonyl] amino } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-6-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-l-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2, 8 -diazaspiro [4.5] dec-2 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N- [4 -(2,7 -diazaspiro [4.5] dec-7 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide; N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N- [4 -( 1 , 8 -diazaspiro [4.5] dec- 8 -ylcarbonyl)phenyl] -5 -fluoro- 1 , 3 -dihydro -2H- isoindole-2-carboxamide;
N-[4-(2,6-diazaspiro[3.4]oct-2-ylcarbonyl)phenyl]-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-( 1 ,6-diazaspiro [3.5]non- 1 -ylcarbonyl)phenyl] -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-5 -fluoro- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(2-oxa-7-azaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[6-(3-acetylphenyl)-4-(3-hydroxypropyl)-2-oxoquinolin-l(2H)-yl]butyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-1 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-(acetarrddomemyl)-N-{4-[(cyclopentylacetyl)amino]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{5-[2-(2-chlorobenzyl)-l,3-thiazol-4-yl]-2-thienyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(4-fluorophenyl)butyl]-5-(hydroxymethyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl] methyl } carbamoyl)phenyl] - 1 -dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( 1 -isobutyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydro-2H-pyran-4-ylmethyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 -dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylmethyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(cyclopentylacetyl)amino]phenyl}-5-(2-hydroxypropan-2-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl {4-[(13-dmydro-2H-isoindol-2-ylcarbonyl)amino]benzyl}carbamate; N-{ 4-[(cyclopentylacetyl)amino]phenyl } - 1 ,3-dmydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(cyclopentylacetyl)amino]phenyl } -5-(methoxymethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(5- { [(tetrahydrofuran-2-ylmethyl)amino]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl] - l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- {5-[(4-methoxypiperidin- 1 -yl)methyl]- 1 ,2,4-oxadiazol-3-yl Jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(5- { [4-(2-methoxyethyl)piperazin- 1 -yl]methyl } - 1 ,2,4-oxadiazol-3-yl)phenyl]- l,3-dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [ 1 -(morpholin-4 -yl)cyclopentyl] methyl } carbamoyl)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-pentanoylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(l-acetylpiperidin-4-yl)oxy]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butyrylpiperidin-4-yl)oxy]phenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-4-yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(cyclopentylacetyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[( 1 -acetylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 6- [( 1 -isobutyrylpiperidin-4-yl)oxy]pyridin-3-yl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [ 1 -(3-methylbutanoyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(4,4,4-trifluorobutanoyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(methoxyacetyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopropylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopropylacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6 - { [ 1 -(cyclobutylcarbonyl)piperidin-4-yl] oxy } pyridin-3 -yl) -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclopentylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(6-{ [l-(cyclopentylacetyl)piperidin-4-yl]oxy}pyridin-3-yl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(6- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy }pyridin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
tert-butyl (2- { 4- [( 1 ,3-dihydro-2H-isoindol-2- ylc arbonyl) amino] phenyl } ethyl)c arb amate ;
N-(4-{ l-[(2R)-tetr ahydrofuran-2-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin -4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(lS)-l-(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
5-cyano-N- { 4-[(tetrahydrofuran-3-ylmethyl)sulfamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tetrahydrofuran-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(3 -phenylpropanoyl)pyrrolidin- 3 -yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- [4 -( { 1 - [(4-methoxyphenyl) acetyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)pyrrolidin-3 -yl] oxy } phenyl) -1,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(l-benzoylpyrrolidin-3-yl)oxy]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -( { 1 - [( 1 -methylcyclopropyl)carbonyl] pyrrolidin-3 -yl } oxy)phenyl] -1,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(cyclobutylcarbonyl)pyrrolidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -acetylpyrrolidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine-
2-carboxamide;
N-(4- { [ 1 -(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethoxyacetyl)pyrrolidin-3-yl]oxy }phenyl)-l ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ 1-[(1 -methylpiperidin-4-yl)carbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin -4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
tert-butyl [( 1 - { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl } azetidin-3- yl)methyl]carbamate;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(morpholin-4-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-(4- { [(2-methoxyethoxy)acetyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(2,3-dimethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2,2-dimethylpropanoyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ [l-(3 -dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(tricyclo[3.3.1.1~3,7~]dec-l-ylacetyl)azetidin-3-yl]oxy}phenyl)-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [(4-methoxycyclohexyl)carbonyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [4-(acetylamino)phenyl] sulfonyl } amino)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(propylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-propylphenyl)sulfonyl]amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(butylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3 ,4-c]pyridine-2- carboxamide;
N-{4-[({ [(lS,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-l- yl]methyl } sulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(ethylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(benzylsulfonyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(4-fluorophenyl)sulf nyl] amino } phenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(thiophen-2-ylsulfonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine- 2-carboxamide;
N-[4-(l,7-diazaspiro[4.4]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,6-diazaspiro[4.5]dec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,7-diazaspiro[4.5]dec-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,
9-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,8-diazaspiro[5.5]undec-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-[4-(l,8-diazaspiro[5.5]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.6]undec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-4,8-diazaspiro[5.5]undec-4-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,8-diazaspiro[4.5]dec-8-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,7-diazaspiro[3.5]non-7-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l,6-diazaspiro[3.5]non-l-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(2,5-diazaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(5-oxa-2-azaspiro[3.4]oct-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(6-oxa-2-azaspiro[3.5]non-2-ylcarbonyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(hexahydro-5H-furo[2,3-c]pyrrol-5-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(tetrahydro-lH-furo[3,4-c]pyrrol-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(hexahydrofuro[3,4-c]pyridin-5(3H)-ylcarbonyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [ 1 -(Ν,Ν-dimethylglycyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-3 -ylacetyl) amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l-en-l-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 , 1 -dioxidotetrahydrothiophen-3 -yl)carbonyl] amino } cyclohex- 1 -en- 1 - yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(4,4-difluorocyclohexyl)carbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 4 - [(tetrahydrofuran-2-ylcarbonyl) amino] cyclohex- 1 -en- 1 -yl } phenyl) -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(piperidin- 1 -ylsulfonyl)phenyl]- 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
5-fluoro-N-(4-{ [l-(l,3-thiazol-2-yl)propan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4,4-difluorocyclohexyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- lH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5-fluoro- l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; Nalpha-(4-{ [(5-fluoro-13-dmydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-D- phenylalanin amide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yl}carbonyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl}phenyl)-5- fluoro-l,3-dihydro-2H-isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl} -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(3,5 -dimethyl- lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5-fluoro- 1,3- dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(3S)- 1 -methyl-2-oxoazepan-3-yl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(5-methyl-lH-pyrazol-l-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-chloro-lH-pyrazol-l-yl)ethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-5,7- dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- bjpyridine -6-carboxamide;
N-[4-({4-[2-(2-hydroxyethoxy)ethyl]piperazin-l-yljcarbonyl)phenyl]-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine -6-carboxamide;
N-{4-[(2-carbamoylbenzyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4- bjpyridine -6-carboxamide;
N-{4-[bis(2-methoxyethyl)carbamoyl]phenylj-5,7-dihydro-6H-pyrrolo[3,4- bjpyridine -6-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 ,7-dihydro-6H-pyrrolo [3,4- bjpyridine -6-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyljphenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(pyrazin-2-yl)piperazin-l-yl]carbonyljphenyl)-5,7-dihydro-6H-pyrrolo[3,4- bjpyridine -6-carboxamide;
Nalpha-{4-[(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-ylcarbonyl)amino]benzoylj-L- phenylalanin amide; N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl }phenyl)-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N- { 4- [(4-cyclohexylpiperazin- 1 -yl)carbonyl]phenyl } -5,7-dihydro-6H-pyrrolo [3 ,4- b]pyridine-6-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-[4-(4,5,6,7-tetrahydro-lH-indazol-5-ylcarbamoyl)phenyl]-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [(3-methyl- 1 ,2-oxazol-5-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N- { 4-[methyl(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrazol-3-yl)methyl]carbamoyl}phenyl)-l,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N- {4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(l -methoxybutan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [benzyl(methyl)carbamoyl]phenyl } -5-fluoro- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl} -5-fluoro- l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(pyridin-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropyle thy 1] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(l-methylcyclopropyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(thiophen-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole-
2-carboxamide; N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(2S)- 1 -methoxypropan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrrol-2-yl)methyl] carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyljphenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -amino- 1 -oxobutan-2-yl] carbamoyl }phenyl)-5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl]-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-2-methylbutyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; 5-fluoro-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5-fluoro-1 -dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l-cyanoethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-memoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(3-memyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[memyl(3-memylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(l-memyl-lH-pyrazol-3-yl)memyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [4-(dimemylarrdno)butyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(l,3-thiazol-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -methoxybutan-2-yl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-{4-[(4-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(2-ethoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{ 4-[( 1 -cyanocyclopropyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(5-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(4-methyl-l,3-thiazol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-{4-[(2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [(lR)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(thiophen-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [(lS)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(1 -methyl- lH-pyrrol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[methyl(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxyethyl)(methyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{ 4-[( 1 -cyanoethyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6 -carboxamide ; N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[methyl(propyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b] pyridine-6-carboxamide;
methyl 1 - { 4- [( 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } azetidine-3-carboxylate;
N-(4- { 3-[(3-methylbutyl)carbamoyl]azetidin- 1 -yl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydrofuran-2-ylmethyl)carbamoyl] azetidin- 1 -yljphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 3-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [3 -(benzylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c] pyridine-2-carboxamide;
N- { 4- [3 -(cyclopentylcarbamoyl)azetidin- 1 -yljphenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 3-[(cyclopentylmethyl)carbamoyl] azetidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{3-[(2-methoxyethyl)carbamoyl]azetidin-l -yljphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3-methylbutanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopentylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-2-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(pyrrolidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(pyrazin-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4,4-difluorocyclohexyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-memyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(6- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({2-[(dimethylamino)methyl]benzyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l,3-oxazol-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [2-(furan-2-yl)-2-(pyrrolidin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- {4-[l-(tetrahydrofuran-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl }- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(4-fluorobenzyl)(3-methylbutanoyl)amino]butyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(9-chloro-5-oxo-2,3,3a,4,4a,5-hexahydro-6H-furo[2',3':2,3]cyclobuta[l,2- c]quinolin-6-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[7-chloro-l-(2-hydroxyethyl)-3-oxo-l,3-dihydrocyclobuta[c]quinolin-4(2H)- yl]butyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[( 1 -acetylpiperidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N- { 4- [( 1 -butanoylpiperidin-3 -yl)oxy] phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4 - { [ 1 -(methoxyacetyl)piperidin-3 -yl] oxy } phenyl) - 1 , 3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(2-methylbutanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4-{ [l-(3 -trifluoropropanoyl)piperidin-3-yl]oxy}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclobutylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-2-ylcarbonyl)piperidin-3-yl]oxy jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydro-2H-pyran-4-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylacetyl)piperidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [3-(3,5 -dimethyl- IH-pyrazol- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 ,3 -thiazol-2-yl)ethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(2,2-difluoroethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(5-methyl-l, 2-oxazol-3-yl)methyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-4-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,5 -dimethyl- IH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -L- phenylalanin amide;
N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(thiophen-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(5-methyl- IH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(3-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methyl- lH-pyrazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [2-(acetylamino)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -methoxybutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pyrimidin-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-( 1 H-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-methylbutyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyljphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]butylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]butylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l-(cyclohexylcarbonyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}butyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(propan-2-yloxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(4,4,4-trifluorobutanoyl)piperidin-4-yl]butylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(3-ethoxypropanoyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(1 -acetylpiperidin-4-yl)carbonyl] amino jphenyl)- 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(ethoxyacetyl)aminojphenyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N- { 4- [(tetrahydrofuran-2-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(cyclopentylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{7-oxo-7-[(3-phenylpropyl)amino]heptyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(bicyclo[2.2 ]hept-2-ylacetyl)amino]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-{ 4-[( 1 ,3-thiazol-5-ylcarbonyl)amino]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(4-0X0-4, 5,6,7-tetrahydro-l-benzofuran-3-yl)carbonyl] amino jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{2-[(3-methylbutanoyl)amino]ethyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{2-[(4-methylpentanoyl)amino]ethyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(ethoxy acetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole-2- carboxamide;
N-[4-(2- { [(2-methoxyethoxy)acetyl] amino } ethyl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-2-ylcarbonyl) amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(cyclopentylcarbonyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4 - { 2 - [(cyclopentylacetyl) amino] ethyl } phenyl) - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[2-(benzoylamino)ethyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{2-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]ethyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydro-2H-pyran-4 -ylacetyl)amino] ethyl } phenyl) -1,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 2 - [(tetrahydrofuran-3 -ylacetyl) amino] ethyl } phenyl) -1,3 -dihydro-2H-isoindole- 2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-L-prolyl)azetidin-3-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[( 1 -propanoylazetidin-3-yl)oxy]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-ethylbutanoyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N-(4-{ [l-(pent-4-ynoyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)azetidin-3 -yl]oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethylglycyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(N,N-dimethyl-beta-alanyl)azetidin-3 -yljoxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrrolidin- 1 -ylacetyl)azetidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(pyrrolidin-l-yl)propanoyl]azetidin-3-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { 1 - [3-(piperidin- 1 -yl)propanoyl] azetidin-3 -yl } oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[(4-methylpiperazin- 1 -yl)acetyl] azetidin-3-yl }oxy)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(4-methylpiperazin-l-yl)propanoyl]azetidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopropylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-cyclopentylethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [ 1 -(3,3-dimethylbutyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclohexylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(3-methylbutyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopentylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(tetrahydrofuran-2-ylmethyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpropyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [l-(butylsulfonyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(cyclopropylsulfonyl)piperidin-4-yl] oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(phenylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-({ l-[(4-fluorophenyl)sulfonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(ethylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propan-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(benzylsulfonyl)piperidin-4-yl]oxyjphenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(propylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(thiophen-2-ylsulfonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-2-methylbutanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-({ l-[(4,4-difluorocyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(5-oxo-D-prolyl)piperidin-4-yl]oxy}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2,2-dimethylpropanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-methylpentanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(2-ethylbutanoyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4 - { [ 1 -( 1 H-pyrrol-2-ylcarbonyl)piperidin-4-yl] oxy jphenyl) -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [l-(l,2 -oxazol-5 -ylcarbonyl)piperidin-4-yl] oxy } phenyl) -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyridazin-3-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrazin-2-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(pyrimidin-4-ylcarbonyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[(5-methylpyrazin-2-yl)carbonyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ l-[3-(piperidin-l-yl)propanoyl]piperidin-4-yljoxy)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ 1 -[3-(4-methylpiperazin- 1 -yl)propanoyl]piperidin-4-yl }oxy)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
benzyl trans-3-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl)amino]cyclobutanecarboxylate;
N-[4-(4- { [(4-methylpiperazin- 1 -yl)acetyl] amino jcyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[4-(benzoylamino)cyclohex- 1 -en- 1 -yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [( 1 -methylpiperidin-4-yl)carbonyl] amino jcyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(1,1 -dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl] amino } cyclohex- 1 -en- l-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3R)-tetrahydrofuran-3-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(4- { [(3S)-tetrahydrofuran-3 -ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 - (4 - { [(2S) -2 -methylbutanoyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { 3 - [(3 -methylbutanoyl) amino] oxetan-3 -yl } phenyl) - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
tert-butyl 4-({4-[(l,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2- ylcarbonyl) amino] phenyl } sulfonyl)piperidine- 1 -carboxylate;
N-{ 4-[4-(propylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(2-methoxyethyl)carbamoyl]piperidin- 1 -yl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(cyclopentylmethyl)carbamoyl]piperidin- 1 -yl } phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(l ,4-dioxan-2-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [4-(cyclopentylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3 -dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [4-(tetrahydro-2H-pyran-4-ylcarbamoyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(morpholin-4-ylcarbonyl)piperidin- 1 -yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[4-(cyclopropylcarbamoyl)piperidin-l-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- {4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]piperidin- 1 -yl } phenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- {4-[(2-hydroxy-2-methylpropyl)carbamoyl]piperidin- 1 -yl jphenyl)- 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[4-(butan-2-ylcarbamoyl)piperidin- 1 -yl]phenyl } -1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yljphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { (4R)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { (4S)-4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-benzoylazetidin-3-yl)butyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-benzoylazetidin-3-yl)butyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[trans-3-(benzylcarbamoyl)cyclobutyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{trans-3-[(2-phenylethyl)carbamoyl]cyclobutylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { trans-3- [(3-phenylpropyl)carbamoyl] cyclobutyl } - 1 ,3 -dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methyl- 1 ,3-oxazol-4-yl)carbonyl]- 1 ,2, 3, 6-tetr ahydropyridin-4- yljphenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(furan-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ l-[(2E)-3-(furan-2-yl)prop-2-enoyl] -1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,3-oxazol-5-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3,3,3-trifluoropropanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,5 -dimethyl- 1 H-pyrazol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methoxycyclohexyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,3-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2,2-difluorocyclopropyl)carbonyl] -1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(lH-pyrazol-5-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tert-butoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-l, 2,4-triazol- 1 -yl)propanoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-ethoxypropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-hydroxy-3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-pyrrol- l-yl)propanoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -methylcyclopropyl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methylpropoxy)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l-methylprolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 -hydroxycyclopropyl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-{4-[l-(cyclopropylacetyl)-l,2 ,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l - { [1 -(methoxymethyl)cyclopropyl]carbonyl } - 1 ,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(methylsulfonyl)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -acetyl- 1 ,2, 3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4- [1 -(eye loprop ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-4-methylpent-2-enoyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-methoxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopent- 1 -en- 1 -ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 - dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(thiophen-3-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -propanoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2,2-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrrol-2-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(2,2-dimethylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(4-methylhexanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-dimethylcyclopropyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-5-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(cyclobutylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } -1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(piperidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[2-(pyrrolidin- 1 -yl)propanoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2-methoxyethoxy)acetyl] amino } cyclohexyl)phenyl] - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -(trans-4- { [(2 -methoxyethoxy) acetyl] amino } cyclohexyl)phenyl] -1,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino }cyclohexyl)phenyl]- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } eye lohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(cis-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohexyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(trans-4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclone xyl)phenyl] -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl }pyridazin-3-yl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3R)-1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclobutylcarbonyl)pyrrolidin-3-yl] oxy jphenyl)- 1 ,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3R)-l-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-[4-({(3R)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(3R)- 1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(3-methylbutanoyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclobutylcarbonyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({(3S)-l-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yljoxy)phenyl]-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(3S)-1 -(cyclopropylacetyl)pyrrolidin-3-yl]oxy jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(6-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyljpyridazin-3-yl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 6-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]pyridazin-3-yl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(cyclopentylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{6-[(tetrahydrofuran-3-ylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{6-[(bicyclo[2.2.1]hept-2-ylmethyl)carbamoyl]pyridazin-3-ylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(2-methylpropanoyl)amino]cyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(2-methylpropanoyl)amino]cyclohexyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(cyclohexylcarbonyl)amino]cyclohexyljphenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(cyclohexylcarbonyl)aminojcyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { trans-4- [(cyclopropylacetyl)aminojcyclohexyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{cis-4-[(cyclopropylacetyl)amino]cyclohexyl jphenyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- {4-[(2-methylpropanoyl)amino]cyclohex- 1 -en-1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(4- { [(2R)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en- 1 -yl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(4- { [(2S)-tetrahydrofuran-2-ylcarbonyl] amino } cyclohex- 1 -en-1 -yl)phenyl]- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(cyclopentylacetyl)amino]cyclohex- 1 -en- 1 -yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4 - { 4 - [(cyclopropylacetyl)amino] cyclohex- 1 -en- 1 -yl } phenyl) - 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { 4- [(2-hydroxy-2-methylpropanoyl)amino] cyclohex- 1 -en- 1 -yl } phenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- {4-[(tetrahydro-2H-pyran-4-ylcarbonyl)amino]cyclohex- 1 -en- 1 -yljphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{4-[(cyclohexylcarbonyl)amino]cyclohex-l -en-1 -yljphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; and pharmaceutically acceptable salts thereof.
10. The compound of claim 1, selected from the group consisting of:
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamo yljphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonylj- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 -dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxarnide; N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-1 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
11. The compound of claim 1, selected from the group consisting of:
N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
12. The compound of claim 2, selected from the group consisting of:
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [4-(aminomethyl)benzyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxarnide; 5-fluoro-N- { 4-[(pyridin-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] -5-fluoro- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(3,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4- [(3 -phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2,3-dihydro- 1 ,4-benzodioxin-5-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(3-methylbutyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide; N-{4-[(2-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-{4-[(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(2-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N-(4-{ [3-(2-oxopyrrolidin-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5-methyl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-fluorobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-oxopyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [4-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-fluoro-5-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; 5-methoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-nitro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; 5-methyl-N-{4-[(3-methylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide; N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(2,3-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-methoxy-N- { 4-[(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(pyridin-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [2-(2-thienyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3-methylbutyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(6-aminohexyl)carbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide;
4-chloro-N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2-thienyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 ,3-benzodioxol-5-ylmethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(benzylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[(3-butoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(3,4-dihydroxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(3-propoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-furylmethyl)carbamoyl]phenyl}-1 -dmydro-2H-isoindole-2-carboxamide; N- { 4- [(3-hydroxy-2-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methylbutyl)carbamoyl]phenyl}-5-(trifluoromethyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methyl-lH-indazol-5-yl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,5-dimethoxyphenyl)ethyl]carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
methyl 5-({4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl} amino)- 1H- indazole-3-carboxylate;
N-(4- { [2-(2-oxopyrrolidin- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(lH-indol-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethyl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(2,3-dihydro- 1 ,4-benzodioxin-6-ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(5-methoxy- lH-indol-3-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(3-aminobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(2-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-hydroxy-4-methylpentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-propoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3,4,5-trimethoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-methylpiperidin- 1 -yl)carbonyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N- [4 -( { 2- [4-(dimethylamino)phenyl] ethyl } carbamoyl)phenyl] -1,3 -dihydro -2H- isoindole-2-carboxamide;
N-(4-{ [3-(trifluoromethoxy)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(lR)-3-hydroxy- 1 -phenylpropyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[(3-fluoro-4-methoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,3-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(2-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(isobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(l ,3-benzodioxol-5-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(2-methoxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(2-isopropoxyethyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
4-chloro-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-methoxypropyl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(4-fluorophenyl)emyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2,5-dicarboxamide; N- { 4- [(2-phenoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(4-hydroxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-fluorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-( { 1 - [(3S)-tetrahydrofuran-3 -yl] - 1 H-pyrazol-4-yl } carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-methyl-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-phenylethyl)carbamoyl]phenylj-1 -dmydro-2H-isoindole-2-carboxamide; N-(4- { [2-(2,4-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(methylthio)propyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-ethoxyethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [(2-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-({ 4-[(trifluoromethyl)thio]benzyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3,4-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [3-(lH-imidazol-l-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } -5-(trifluoromethyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [4-(hydroxymethyl)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l,3-benzodioxol-5-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -isopropyl- lH-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(4-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -ethyl- 1 H-pyrazol-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,5-dimethoxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -benzylpiperidin-4-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(5-acetamido-2-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(3,5-dimethoxyphenyl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-
2-carboxamide; N-[4-({ 2-[3-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-( 1 H-imidazol-4-yl)ethyl] carbamoyl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1R)- 1 -(3-cyanophenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4-cyanophenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(4-chlorophenyl)ethyl]carbamoyl jphenyl)- 1 , 3-dihydro-2H-iso indole-2- carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(pyridin-2-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(cyanomethyl)carbamoyljphenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(cyclohexylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{ 4-[(3-hydroxyphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimethylamino)phenyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(phenylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(4-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [2-(diemylamino)ethyl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-aminophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [l-(3-chlorobenzyl)-lH-pyrazol-4-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-hydroxy-6-methylphenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3-hydroxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(5-fluoropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tert-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [(3-methylbutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(3S)-1 -benzylpyrrolidin-3-yl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(3-fluorophenyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(cyclopropylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(methylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [3-(dimemylamino)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pentan-2-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(pentan-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-[4-(cyclobutylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [ 1 -(4-fluorophenyl)- lH-pyrazol-4-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(l -phenyl- lH-pyrazol-4-yl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide; N-[4-({ 2-[4-(trifluoromethyl)phenyl]ethyl }carbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(sec-butylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -methoxypropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{ 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(lR)-2-hydroxy- 1 -phenylethyljcarbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4- { [(2R)- 1 -hydroxy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -hydroxybutan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(prop-2-yn- 1 -ylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; 5,6-dimethoxy-N- { 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [3-(4-chlorophenoxy)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(trifluoromethoxy)phenyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(4-phenyl- 1 ,3-thiazol-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
methyl 2-{ [4-(propylcarbamoyl)phenyl]carbamoyljisoindoline-5-carboxylate;
2-{ [4-(propylcarbamoyl)phenyl]carbamoyljisoindoline-5-carboxylic acid;
5-amino-N- [4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; 5-(hydroxymethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5-(aminomethyl)-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(2-hydroxy-2-methylpropanoyl)amino] -N- [4-(propylcarbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-acetamido-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
5- [(N,N-dimethylglycyl)amino] -N- [4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-3-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(propylcarbamoyl)phenyl]-5-(lH-pyrazol-4-yl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-[(methoxyacetyl)amino]-N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-[(methylsulfonyl)amino] -N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-bromo-N-[4-(propylcarbamoyl)phenyl]-13-dihydro-2H soindole-2-carboxamide; N-{4-[(3,5-dimethoxybenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-chlorobenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(3-phenylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{ 4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-methylbutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
5-fluoro-N-[4-(propylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-(4- { [(3R)-tetrahydrofuran-3-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(5-chloropyridin-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3-hydroxy-4-methoxyphenyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2,4-dimethoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [4-(2-oxopyrrolidin- 1 -yl)benzyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [(lS,2S)-2-hydroxy-2,3-dihydro-lH-inden-l-yl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide; N-(4-{ [(lmydroxycyclopropyl)methyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(propylcarbamoyl)phenyl] -5-vinyl- 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- d]pyrimidine-6-carboxamide;
N-(4-{ [(3-phenylpropyl)amino]carbonyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- d]pyrimidine-6-carboxamide;
5-fluoro-N-[4-({ [(2S)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-({ [(2R)-tetrahydrofuran-2-ylmethyl] amino }carbonyl)phenyl]- 1,3- dihydro-2H-isoindole-2-carboxamide;
N- [4 -( { [( 1 S) -2-hydroxy- 1 -phenylethyl] amino } carbonyl)phenyl] -1,3 -dihydro -2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-3-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(propylamino)carbonyl]phenyl}-5-pyridin-4-yl-l,3-dihydro-2H-isoindole-2- carboxamide;
N5-(2-methoxyethyl)-N2-{4-[(propylamino)carbonyl]phenyl}-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4 - { [(3 -methylbutyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4 - { [(tetrahydrofuran-3 -ylmethyl) amino] carbonyl } phenyl) -5,7 -dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-[4-( { [( 1 S)-2-hydroxy- 1 -pyridin-2-ylethyl] amino } carbonyl)phenyl] - 1 ,3 -dihydro- 2H-isoindole-2-carboxamide; 5-( 1 ,2-dihydroxyethyl)-N- { 4- [(propylamino)carbonyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [6-(benzoylarnino)hexyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-({4-[(benzoylamino)methyl]benzyl}carbamoyl)phenyl]-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N5-[2-(dimethylamino)ethyl]-N2-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2,5-dicarboxamide;
5-(morpholin-4-ylcarbonyl)-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(isobutoxycarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; 5-fluoro-N- { 4-[(tetrahydro-2H-pyran-2-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl} - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-l-hydroxy-4-methylpentan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(2S)- 1 -hydro xy-4-(methylthio)butan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(2S,3S)-1 -hydroxy-3-methylpentan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xypropan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [(2S R)-13-dmydroxybutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-1 -hydro xyhexan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-1 -hydro xypentan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 S,2S)-2-hydroxycyclopentyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4 - { [( 1 S ,2R) -2-hydroxycyclopentyl] carb amoyl } phenyl) -1,3 -dihydro -2H-isoindole- 2-carboxamide;
N-(4- { [(2S)- 1 -cyclohexyl-3-hydroxypropan-2-yl] carbamoyl jphenyl)- 1 ,3 -dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ (2R)- 1 -hydroxy-3-[(4-methylbenzyl)thio]propan-2-yl }carbamoyl)phenyl] -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { [(IS)- 1 -(4-tert-butylphenyl)-2-hydroxyethyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-methoxy-N-[4-(propylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-memyl-N-[4-(propylcarbamoyl)phenyl]-l,3-dmydro-2H-isoindole-2-carboxamide; N-[4-(propylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4-{ [(2S)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l -hydro xy-4-methylpentan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl] carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-(hydroxymethyl)-N- { 4-[(3-methylbutyl)carbamoyl]phenyl} - 1 ,3 -dihydro -2H- isoindole-2-carboxamide;
N-(4-{ [(lS)-2-hydroxy-l-(pyridin-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-(4-{ [(3R)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide; 5-fluoro-N-(4-{ [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl}phenyl)-1 -dihydro- 2H-isoindole-2-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(4-hydroxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { [(2S)- 1 -hydro xy-3-methylbutan-2-yl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [( 1 -hydro xy-2-methylpropan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [(2S)-2-hydroxypropyl] carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(piperidin-l -yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [3-(2-oxopyrrolidin- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(3S)-tetrahydrofuran-3-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2-isopropoxyethyl)carbamoyl]phenylj-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl jphenyl)- l,3-dihydro-2H -pyrrolo[3, 4- c]pyridine-2-carboxamide;
N- { 4- [(cyclopropylmethyl)carbamoyljphenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-[4-(isobutylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-[4-(butylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide; N-{ 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl] - 1 ,3-dihydro-2H-pyrrolo [3,4-c]pyridine-2- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-thienylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{4-[(3-isopropoxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N- { 4- [(3-isobutoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-{ 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-{ 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [3-(dimethylamino)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine- 2-carboxamide;
N-(4- { [4-(dimethylamino)butyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; N- { 4- [(pyridin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N- { 4- [(pyrimidin-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [2-(pyridin-3-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { [2-(4-methylpiperazin-l -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-methoxy- 1 -phenylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-({ [(4S)-2,2-dimethyl-l,3-dioxolan-4-yl]methyljcarbamoyl)phenyl]-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-({ [(4R)-2,2-dimethyl-l,3-dioxolan-4-yl]methyljcarbamoyl)phenyl]-l,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyljcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2R)-butan-2-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(3-methyloxetan-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[(cyclopentylmethyl)carbamoyl]phenylj - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- { 4-[(l ,3-thiazol-5-ylmethyl)carbamoyl]phenyl }- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [( 1R) -3 -hydroxy- 1 -phenylpropyljcarbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(4-methylphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[(l ,3-dihydroxypropan-2-yl)carbamoyl]phenylj - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-2-hydroxypropyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; 5-cyano-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2R)-l-hydroxy-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(2S)-tetrahydrofuran-2-ylmemyl]carbamoyl jphenyl)- 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2-(4-methylpiperazin- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 S)-2-hydroxy- 1 -phenylethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(4-hydroxybutyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N-(4-{ [(2S)-2-hydroxypropyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- {4-[(3-furylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-cyano-N- {4-[(tetrahydro furan-2-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(2R)-tetrahydrofuran-2-ylmethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N- {4-[(tetrahydro furan-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4- { [(lR)-2-hydroxy- 1 -phenylethyljcarbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N-(4-{ [(2S)-1 -hydro xybutan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(2,3-dihydroxypropyl)carbamoyl]phenylj - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-4-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [2 -hydroxy- 1 -(pyridin-2-yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(l -hydroxy-4-methylpentan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; 5-cyano-N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-cyano-N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-cyano-N- { 4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-
2H-isoindole-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1,1 -dioxidotetrahydrothiophen-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [(pyrrolidin-3 -ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-pyrrolo [3,4- c]pyridine-2-carboxamide;
N-(4-{ [(3S)-pyrrolidin-3-ylmethyl]carbamoyl jphenyl)- l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpyrrolidin-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 -methylpiperidin-4-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-fluoro-N-{4-[(l-oxa-8-azaspiro[4.5]dec-2-ylmethyl)carbamoyl]phenylj-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({ [(3R)-l-isobutyrylpyrrolidin-3-yl]methyljcarbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [(3R)-l-benzoylpyrrolidin-3-yl]methyljcarbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-( { [ 1 -(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl] methyl } carbamoyl)phenyl] - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [l-(methylsulfonyl)pyrrolidin-3-yl]methyljcarbamoyl)phenyl]-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- [4 -( { [ 1 -(morpholin-4 -yl)cyclopentyl] methyl } carbamoyl)phenyl] -1,3 -dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-({ [3-(hydroxymethyl)oxetan-3-yl]methyl}carbamoyl)phenyl]-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { [(1 S)- 1 -(4-fluorophenyl)-2-hydroxyethyl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1 S)-2-hydroxy- 1 -(4-methoxyphenyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [(IS)- l-(l,3-benzodioxol-5-yl)-2-hydroxyethyl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -oxa-8-azaspiro [4.5]dec-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-oxa-8-azaspiro[4.5]dec-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[(2-oxa-9-azaspiro[5.5]undec-3-ylmethyl)carbamoyl]phenylj-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-fluoro-N-(4-{ [l-(l,3-thiazol-2-yl)propan-2-yl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(4,4-difluorocyclohexyl)carbamoyl]phenylj-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- IH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5-fluoro- l,3-dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyljphenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(4-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide; Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-D- phenylalanin amide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl}phenyl)-5- fluoro-l,3-dihydro-2H-isoindole-2-carboxamide;
Nalpha-(4-{ [(5-fluoro-l,3-dihydro-2H-isoindol-2-yl)carbonyl]amino}benzoyl)-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [3-(methylcarbamoyl)phenyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl} -5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5-fluoro-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ [(lR)-2-amino-2-oxo-l-phenylethyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3-methoxybenzyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-(3,5 -dimethyl- lH-pyrazol- 1 -yl)ethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide; 5-fluoro-N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4- { [3-(piperidin- 1 -yl)propyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(5-methyl-lH-pyrazol-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(4-chloro-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4- { [ 1 -(3,5 -dimethyl- IH-pyrazol- 1 -yl)propan-2-yl]carbamoyl }phenyl)-5, 7- dihydro-6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(4-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [3-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2-carbamoylbenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } -5 ,7-dihydro-6H-pyrrolo [3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
Nalpha-{4-[(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-ylcarbonyl)amino]benzoyl}-L- phenylalanin amide;
N-(4-{ [(2R)-l-amino-4-methyl-l-oxopentan-2-yl]carbamoyl}phenyl)-5,7-dihydro- 6H-pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-tert-butoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-methoxybenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-(4-{ [2-(4-methylpiperazin-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [4-(morpholin-4-yl)benzyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [3-(piperidin-l-yl)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-[4-(4,5,6,7-tetrahydro-lH-indazol-5-ylcarbamoyl)phenyl]-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
5-fluoro-N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(3-methyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -cyanobutan-2-yl]carbamoyl}phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2R)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(lH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrazol-3-yl)methyl]carbamoyl jphenyl)- 1,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(l -methoxybutan-2-yl)carbamoyl]phenyl} - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } -5-fluoro- 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl}phenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(3-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methylpropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(pyridin-3-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropyle thy 1] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [l-(l-methylcyclopropyl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4- [(thiophen-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5-fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- {4-[(4-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- 1,3-dihydro-
2H-isoindole-2-carboxamide;
5-fluoro-N-(4- { [(2S)- 1 -methoxypropan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(l -methyl- lH-pyrrol-2-yl)methyl] carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyljphenyl)-5-fluoro-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [(2S)- 1 -amino- 1 -oxobutan-2-yl] carbamoyl }phenyl)-5 -fluoro- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N- { 4-[(2-methoxyethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(cyclopentylcarbamoyl)phenyl]-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [(2S)-2-methylbutyl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N- { 4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
5-fluoro-N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-[4-(butylcarbamoyl)phenyl]-5-fluoro-1 -dihydro-2H-isoindole-2-carboxarnide;
N-{4-[(l-cyanoethyl)carbamoyl]phenyl}-5-fluoro-l,3-dihydro-2H-isoindole-2- carboxamide;
5-fluoro-N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
5-fluoro-N- { 4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl} - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(3-methoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3,3-dimethylbutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(3-methyl-l,2-oxazol-5-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide; N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [(l-memyl-lH-pyrazol-3-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [4-(dimemylamino)butyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [l-(l,3-thiazol-2-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(l-methoxybutan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(2-ethoxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(6-methoxypyridin-3-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(l-cyanocyclopropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4-{ [2-(5-methyl-lH-pyrazol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(4-methyl-l,3-thiazol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(3-hydroxypropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-{4-[(2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide; N-(4-{ [(lR)-l-cyclopropylethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl }phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(thiophen-2-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-(4- { [(1 S)- 1 -cyclopropylethyl] carbamoyl }phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(4-methoxybutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine- 6-carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [(2S)-l-methoxypropan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [(1 -methyl- lH-pyrrol-2-yl)methyl]carbamoyl}phenyl)-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-(4-{ [2-(propan-2-yloxy)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [3-(dimemylamino)propyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-(4-{ [2-(lH-pyrrol-l-yl)ethyl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(l-methoxypropan-2-yl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(3-aminobenzyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide;
N-{4-[(tetrahydro-2H-pyran-3-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H- pyrrolo[3,4-b]pyridine-6-carboxamide;
N-{4-[(2-hydroxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine -6-carboxamide; N-[4-(butylcarbamoyl)phenyl]-5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{ 4-[( 1 -cyanoethyl)carbamoyl]phenyl } -5,7-dihydro-6H-pyrrolo[3,4-b]pyridine-6- carboxamide;
N-{4-[(3R)-tetrahydrofuran-3-ylcarbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopentylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(cyclopropylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(pyridin-4-ylmethyl)carbamoyl]phenyl}-5,7-dihydro-6H-pyrrolo[3,4- b]pyridine-6-carboxamide;
N-{4-[(3-memoxy-2,2-dimethylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [(4,4-difluorocyclohexyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2R)-l-cyanobutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxybutyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -(ethylamino)- 1 -oxopropan-2-yl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(1R)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(IS)- 1 -cyclopropylethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(3S)-tetrahydrofuran-3-ylcarbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-3-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(5-methyl- 1 ,3-oxazol-2-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-({2-[(dimethylamino)methyl]benzyl}carbamoyl)phenyl]-l,3-dihydro-2H- isoindole-2-carboxamide; N-(4-{ [(lR)-2-arrdno-2-oxo-l-phenylethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(1 -oxazol-2-ylcarbamoyl)phenyl]-1 -dihydro-2H-isoindole-2-carboxamide; N-[4-(tetrahydro-2H-pyran-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(2,6-dimethylmorpholin-4-yl)ethyl]carbamoyl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [ 1 -(1 -methylcyclopropyl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-(4-{ [2-(furan-2-yl)-2-(pyrrolidin-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [3-(3,5 -dimethyl- IH-pyrazol- 1 -yl)propyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(3S)-l-methyl-2-oxoazepan-3-yl]carbamoyljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [2-(lH-pyrazol-l-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 ,3 -thiazol-2-yl)ethyl] carbamoyl } phenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [l-(furan-2-yl)propan-2-yl]carbamoyljphenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [ 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [(2R)- 1 -amino-4-methyl- 1 -oxopentan-2-yl]carbamoyl jphenyl)- 1,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4-{ [l-(3,5-dimethyl-lH-pyrazol-l-yl)propan-2-yl]carbamoyljphenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[(2,2-difluoroethyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [2-(tetrahydro-2H-pyran-4-yl)ethyl]carbamoyl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[(tetrahydrofuran-2-ylmethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-{4-[(2-methoxy-2-methylpropyl)carbamoyl]phenyl}-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(5-methyl- 1 ,2-oxazol-3-yl)methyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide; N-(4- { [(1 -methyl- 1 H-pyrazol-4-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3,5 -dimethyl- lH-pyrazol- 1 -yl)ethyl] carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
Nalpha- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]benzoyl } -L- phenylalanin amide;
N-(4- { [2-(2-methyl- 1 ,3-thiazol-4-yl)ethyl] carbamoyl Jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ [(2S)-3,3-dimethyl-l-(methylamino)-l-oxobutan-2-yl]carbamoyl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(thiophen-3-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4- { [2-(5-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(3-methyl- lH-pyrazol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[(2S)-butan-2-ylcarbamoyl]phenylj-l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[(3,3-dimethyl-2-oxobutyl)carbamoyl]phenylj-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4- { [(1 -methyl- 1 H-pyrazol-3-yl)methyl] carbamoyl jphenyl)- 1 ,3 -dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-(acetylamino)phenyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -methoxybutan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(tetrahydro-2H-pyran-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(pyrirnidin-4-ylcarbamoyl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxamide; N-(4- { [2-( 1 H-pyrrol- 1 -yl)ethyl]carbamoyl jphenyl)- 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-2-methylbutyl] carbamoyl jphenyl)- l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [( 1 -amino- 1 -oxohexan-2-yl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [(2-amino-2-oxo- 1 -phenylethyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-{ 4-[(3-tert-butoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide; N-(4-{ [3-(memylcarbamoyl)phenyl]carbamoyl}phenyl)-13-dihydro-2H-isoindole-2 carboxamide;
N-(4-{ [(2R)-3-methylbutan-2-yl]carbamoyl}phenyl)-l,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ [(2S)-3-methylbutan-2-yl]carbamoyl}phenyl)-1 -dihydro-2H-isoindole-2- carboxamide;
N-(4- { [2-methyl- 1 -(morpholin-4-yl)propan-2-yl]carbamoyl}phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { [2-methyl-2-(morpholin-4-yl)propyl]carbamoyl } phenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [(2-ethoxypropyl)carbamoyl]phenyl } - 1 ,3-dihydro-2H-isoindole-2-carboxamide; and pharmaceutically acceptable salts thereof.
13. The compound of claim 3, selected from the group consisting of:
tert-butyl 4-{4-[(l,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl}-3,6- dihydropyridine- 1 (2H)-carboxylate;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2- carboxamide;
tert-butyl 4- { 4- [( 1 ,3-dihydro-2H-isoindol-2-ylcarbonyl)amino]phenyl jpiperidine- 1 - carboxylate;
N-[4-(l-butyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-isoindole-2-carboxarnide;
N-[4-(l -isobutyrylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-[4-(l -benzoylpiperidin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N-{4-[l-(4-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(5-oxo-D-prolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-[4-(l -propionyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [ 1 -(2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide; N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(ethoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)-l,3- dihydro-2H-isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-methylbenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(2-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(3-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(4-methoxybenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(2-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(3-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(4-fluorobenzoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(4-chlorobenzoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[3-(dimethylamino)benzoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[4-(dimethylamino)benzoyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide; N-{ 4-[l -(3-thienylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{4-[l-(lH-pyrrol-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(2,5 -dimethyl- 1 H-pyrrol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,3-thiazol-4-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(lH-pyrazol-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 - [(3,5 -dimethyl- 1 ,2-oxazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-2-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-isoindole-2-carboxamide;
N-{4-[l-(pyridin-3-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-
2H-isoindole-2-carboxamide;
N-[4-( 1 -isonicotinoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl] - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-{ 4-[l -(pyridazin-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-{ 4-[l -(pyrimidin-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[3-(piperidin- l-yl)propanoyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-isoindole-2-carboxamide;
N-(4- { 1 -[(4-methylpiperazin-l -yl)acetyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-[4-(l-butyryl-l,2,3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-[4-(l -isobutyryl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -benzoyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide; N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)-l ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [(2-methoxyethoxy)acetyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl } phenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l-isobutyrylpiperidin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole- 2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ 1-[(1 -methylpyrrolidin-3-yl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - l,3-dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(l,4-dioxan-2-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3- dihydro-2H-isoindole-2-carboxamide;
N-(4- { 1 -[(1 -methylpyrrolidin-3-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydrothiophen-3-yl)carbonyl]-l,2,3,6-tetrahydropyridin-4- yl } phenyl)- 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{ 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methoxyethoxy)acetyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4-{ l-[(2R)-tetrahydrofuran-2-ylcarbonyl] -1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2S)-tetrahydrofuran-2-ylcarbonyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -( 1 ,4-dioxan-2-ylcarbonyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-
2-carboxamide;
N-(4-{ l-[(l-methylpyrrolidin-3-yl)carbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jphenyl)- 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-l,3-dihydro-2H- isoindole-2-carboxamide;
N- { 4- [ 1 -(morpholin-4-ylacetyl)piperidin-4-yl]phenyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-(4-{ 1-[(1 -methylpiperidin-4-yl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl}phenyl)-13-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetrahydrofuran-3-ylcarbonyl]-l,2,3,6-tetrahydropyridin-4-yl}phenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-isoindole-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-4-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(Ν,Ν-dimethylglycyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methylpiperazin-l-yl)acetyl]- 1,2,3, 6-tetrahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopentylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydro-2H-pyran-2-ylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(pyrrolidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(pyrazin-2-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
5-cyano-N- { 4-[l -(tetrahydrofuran-3-ylcarbonyl)- 1 ,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- {4-[l-(tetrahydro-2H-pyran-4-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide; 5-cyano-N- { 4-[l -(2-hydroxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4- yl]phenyl } - 1 ,3 -dihydro-2H-isoindole-2-carboxamide;
5-cyano-N- { 4-[l -(morpholin-4-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl }- 1,3- dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(3R)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(3S)-tetr ahydrofuran-3-ylcarbonyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)carbonyl]-l,2,3,6- tetrahydropyridin-4-yl jphenyl)- 1 ,3-dihydro-2H-isoindole-2-carboxamide;
N-(4-{ l-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jphenyl)- l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yljphenyl)-l,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(3R)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl jphenyl)- 1 ,3-dihydro-2H- isoindole-2-carboxamide;
N-(4- { 1 -[(2-methyl- 1 ,3-oxazol-4-yl)carbonyl]- 1 ,2,3,6-tetrahydropyridin-4- yljphenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(furan-3-ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-3-(furan-2-yl)prop-2-enoyl] -1,2,3, 6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l,3-oxazol-5-ylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenylj-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(3,3,3-trifluoropropanoyl)-l,2,3,6-tetrahydropyridin-4-yl]phenylj-l,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,5 -dimethyl- 1 H-pyrazol-3-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yljphenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(4-methoxycyclohexyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4-yljphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,3-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { 1 -[(2,2-difluorocyclopropyl)carbonyl] -1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(lH-pyrazol-5-ylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl} -1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(tert-butoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-l, 2,4-triazol- 1 -yl)propanoyl]- 1,2,3, 6-tetr ahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-ethoxypropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(3-hydroxy-3-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[3-(lH-pyrrol- l-yl)propanoyl]- 1,2, 3, 6-tetr ahydropyridin-4-yl}phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(l -methylcyclopropyl)carbonyl] -1,2,3,6 -tetrahydropyridin-4-yl } phenyl) - l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2-methylpropoxy)acetyl] - 1 ,2, 3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(l-methylprolyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-hydroxy-2-methylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -hydroxycyclopropyl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclopentylcarbonyl)- 1,2,3, 6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l - { [1 -(methoxymethyl)cyclopropyl]carbonyl } - 1 ,2,3,6-tetrahydropyridin-4- yl)phenyl]-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(methylsulfonyl)acetyl] - 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -acetyl- 1,2, 3,6-tetrahydropyridin-4-yl)phenyl]-l,3-dihydro-2H-pyrrolo[3, 4- c]pyridine-2-carboxamide; N-{ 4- [1 -(eye loprop ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2-ethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(5-oxo-L-prolyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2E)-4-methylpent-2-enoyl]- 1,2,3, 6-tetrahydropyridin-4-yl} phenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2-methoxy-2-methylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(cyclopent- 1 -en- 1 -ylcarbonyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 - dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(thiophen-3-ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)-l,2,3,6-tetrahydropyridin-4-yl]phenyl}-l,3-dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-[4-(l -propanoyl- 1 ,2,3,6-tetrahydropyridin-4-yl)phenyl]- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(2,2-dimethylbutanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3 -dihydro- 2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 -methyl- 1 H-pyrrol-2-yl)carbonyl] - 1 ,2,3 ,6-tetrahydropyridin-4-yl jphenyl)- l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(methoxyacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(2,2-dimethylpropanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N- { 4- [ 1 -(4-methylhexanoyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2,2-dimethylcyclopropyl)carbonyl]- 1,2,3, 6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-5-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(cyclobutylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } -1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{ 4-[l -(piperidin- 1 -ylacetyl)- 1 ,2,3,6-tetrahydropyridin-4-yl]phenyl } - 1 ,3-dihydro-
2H-pyrrolo[3,4-c]pyridine-2-carboxamide; N-(4- { 1 -[2-(pyrrolidin- 1 -yl)propanoyl]- 1 ,2,3,6-tetrahydropyridin-4-yl jphenyl)- 1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 - [( 1 ,3 -dimethyl- 1 H-pyrazol-4-yl)carbonyl] - 1 ,2,3,6-tetrahydropyridin-4- yl}phenyl)-l,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
14. The compound of claim 4, selected from the group consisting of:
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-isoindole-2-carboxamide; N- { 4- [ 1 -(pyridin-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l-benzoylpiperidin-4-yl)butyl]-5-cyano-l,3-dihydro-2H-isoindole-2- carboxamide;
N- { 4- [ 1 -(pyridin-2-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H-isoindole-2- carboxamide;
N-[4-(l -benzoylpiperidin-4-yl)butyl] - 1 ,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2- carboxamide;
N-{4-[l-(2-chlorobenzoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-2-ylacetyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(1 , 1 -dioxidotetrahydrothiophen-3-yl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(tetrahydrofuran-3-ylacetyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(cyclohexylcarbonyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-(4- { 1 -[(4,4-difluorocyclohexyl)carbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-{4-[l-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4- { 1 -[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl jbutyl)- 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}butyl)-l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(2-methoxyethoxy)acetyl]piperidin-4-yl jbutyl)- l,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide; N-{ 4-[l -(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]butyl } - 1 ,3-dihydro-2H- pyrrolo[3,4-c]pyridine-2-carboxamide;
N-(4-{ l-[(propan-2-yloxy)acetyl]piperidin-4-yl}butyl)-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(cyclopropylacetyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide;
N-{4-[l-(4,4,4-trifluorobutanoyl)piperidin-4-yl]butyl}-l,3-dihydro-2H-pyrrolo[3,4- c]pyridine-2-carboxamide; and pharmaceutically acceptable salts thereof.
15. A composition for treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal-cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, in particular depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis, said composition comprising an excipient and a therapeutically effective amount of a compound of claim 1, or pharmaceutically acceptable salts thereof.
16. A composition for treating inflammatory and tissue repair disorders;
including rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, including breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, ovarian cancer, skin cancer, CNS cancer, bladder cancer, pancreatic cancer, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia, said composition comprising an excipient and a therapeutically effective amount of a compound of claim 1, or pharmaceutically acceptable salts thereof.
17. A method of treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal-cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders including depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis, in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound of claim 1, or pharmaceutically acceptable salts thereof.
18. A method of treating inflammatory and tissue repair disorders including rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, including breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, ovarian cancer, skin cancer, CNS cancer, bladder cancer, pancreatic cancer, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound of claim 1, or pharmaceutically acceptable salts thereof.
19. A method of treating hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension, atherosclerosis, asthma, male erectile dysfunctions, female sexual dysfunction, over-active bladder syndrome, spinal-cord injury, traumatic brain injury, stroke, inflammatory and demyelinating diseases, Alzheimer's disease, pain, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, inflammatory pain, rheumatoid arthritis, osteoarthritis, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, lupus, inflammatory bowel disease, cancer, tumor metastasis, viral infections, bacterial infections, insulin resistance, diabetes, ocular hypertension, preterm labor, atherosclerosis, spinal muscular atrophy, encephalomyelitis, osteoporosis, HIV-1, encephalitis, ischemic CNS disorders, vascular or AD type dementia, glaucoma, retinopathy, benign prostatic hypertrophy, psychiatric disorders, including depression, schizophrenia, obsessive compulsive disorder and bipolar disorder, epilepsy and seizure disorders, for decreasing ischemia-reperfusion injury, myocardial infarct size and myocardial fibrosis, for the prevention of graft failure, and cystic fibrosis in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of claim 1, or pharmaceutically acceptable salts thereof; and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
20. A method of treating inflammatory and tissue repair disorders including rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases; dermatosis, including psoriasis, atopic dermatitis and ultra-violet induced skin damage; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, including breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, ovarian cancer, skin cancer, CNS cancer, bladder cancer, pancreatic cancer, leukemia, lymphoma or Hodgkin's disease, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, and ataxia telengiectasia or spleen cancer in a patient, said method comprising administering to the patient therapeutically effective amount of the compound of claim 1, or pharmaceutically acceptable salts thereof; and a therapeutically effective amount of one additional therapeutic agent or more than one additional therapeutic agent.
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Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013067710A1 (en) 2011-11-11 2013-05-16 Abbott Laboratories Nampt inhibitors
JP2013234180A (en) * 2012-04-13 2013-11-21 Mitsubishi Tanabe Pharma Corp Pharmaceutical application of amide derivative
JP2013544872A (en) * 2010-12-13 2013-12-19 カソリック ユニヴェルシテイト ルーヴェン，ケー．ユー． ルーヴェン アール アンド ディー Novel compounds for the treatment of neurodegenerative diseases
JP2015503594A (en) * 2012-01-09 2015-02-02 エックス−アールエックス，インコーポレーテッド Tryptoline derivative having kinase inhibitory activity and use thereof
WO2014141035A3 (en) * 2013-03-11 2015-04-09 Aurigene Discovery Technologies Limited Fused heterocyclyl derivatives as nampt inhibitors
US9132129B2 (en) 2010-11-15 2015-09-15 Katholieke Universiteit Leuven Antiviral compounds
JP2015528435A (en) * 2012-08-10 2015-09-28 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Pyrazole carboxamide compounds, compositions and methods of use
US9499563B2 (en) 2009-05-15 2016-11-22 Katholieke Universiteit Leuven Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors
US9555039B2 (en) 2011-05-09 2017-01-31 Forma Tm, Llc. Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (NAMPT)
US9673344B2 (en) * 2014-08-07 2017-06-06 Lumeta, Llc Apparatus and method for photovoltaic module with tapered edge seal
WO2018086703A1 (en) 2016-11-11 2018-05-17 Bayer Pharma Aktiengesellschaft Dihydropyridazinones substituted with phenylureas
JP2019073521A (en) * 2013-01-18 2019-05-16 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Phthalazinones and isoquinolinones as rock inhibitors
WO2019149637A1 (en) 2018-01-31 2019-08-08 Bayer Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
RU2732297C2 (en) * 2018-11-14 2020-09-15 Общество с ограниченной ответственностью "Гурус БиоФарм" Derivatives of non-steroid anti-inflammatory agents
WO2021013693A1 (en) 2019-07-23 2021-01-28 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
US20210171513A1 (en) * 2016-03-17 2021-06-10 Checkmate Therapeutics Inc. Novel compound for inhibiting nicotinamide phosphoribosyltransferase and composition containing same
WO2022053651A2 (en) 2020-09-10 2022-03-17 Precirix N.V. Antibody fragment against fap
EP2903618B1 (en) 2012-10-05 2022-06-01 Kadmon Corporation, LLC Rho kinase inhibitors
US11638762B2 (en) 2016-10-18 2023-05-02 Seagen Inc. Targeted delivery of nicotinamide adenine dinucleotide salvage pathway inhibitors
WO2023203135A1 (en) 2022-04-22 2023-10-26 Precirix N.V. Improved radiolabelled antibody
WO2023213801A1 (en) 2022-05-02 2023-11-09 Precirix N.V. Pre-targeting
US11905284B2 (en) 2016-07-01 2024-02-20 Pfizer Inc. 5,7-dihydro-pyrrolo-pyridine derivatives
US11931414B2 (en) 2017-04-27 2024-03-19 Seagen Inc. Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9302989B2 (en) * 2010-11-15 2016-04-05 Abbvie Inc. NAMPT and rock inhibitors
EA026152B1 (en) * 2011-09-01 2017-03-31 Новартис Аг COMPOUNDS AND COMPOSITIONS AS c-kit KINASE INHIBITORS
US9199981B2 (en) * 2011-09-01 2015-12-01 Novartis Ag Compounds and compositions as C-kit kinase inhibitors
WO2014074715A1 (en) * 2012-11-07 2014-05-15 Genentech, Inc. Cyclopropyl amide derivatives
MX364895B (en) 2013-03-13 2019-05-10 Forma Therapeutics Inc Novel compounds and compositions for inhibition of fasn.
WO2015142001A2 (en) * 2014-03-21 2015-09-24 충남대학교산학협력단 Compound having cardiotonic activity and pharmaceutical composition for preventing or treating heart failure, containing same
US9902702B2 (en) 2014-07-15 2018-02-27 Bristol-Myers Squibb Company Spirocycloheptanes as inhibitors of rock
CN106661013A (en) 2014-07-23 2017-05-10 奥瑞基尼探索技术有限公司 4,5-dihydroisoxazole derivatives as NAMPT inhibitors
EP3183248B1 (en) 2014-08-21 2020-11-11 Bristol-Myers Squibb Company Tied-back benzamide derivatives as potent rock inhibitors
WO2016033105A1 (en) 2014-08-29 2016-03-03 The Board Of Regents Of The University Of Texas System Novel capsazepine analogs for the treatment of cancer and other proliferative diseases
US20160108406A1 (en) * 2014-10-08 2016-04-21 University Of Iowa Research Foundation Method of regulating cftr expression and processing
CN106928252B (en) * 2015-12-31 2019-09-27 成都先导药物开发股份有限公司 A kind of compound and the preparation method and application thereof inhibiting ROCK
AR107354A1 (en) 2016-01-13 2018-04-18 Bristol Myers Squibb Co SPIROHEPTAN SALICILAMIDS AND RELATED COMPOUNDS AS ROCK INHIBITORS
WO2017170830A1 (en) * 2016-03-31 2017-10-05 武田薬品工業株式会社 Heterocyclic compound
EP3481828B1 (en) 2016-07-07 2020-09-16 Bristol-Myers Squibb Company Spiro-fused cyclic ureas as inhibitors of rock
WO2018094362A1 (en) * 2016-11-21 2018-05-24 Translational Drug Development, Llc Heterocyclic compounds as kinase inhibitors
WO2018191747A1 (en) * 2017-04-14 2018-10-18 Arizona Board Of Regents On Behalf Of The University Of Arizona Compositions and methods for treating pulmonary arterial hypertension
CA3060080C (en) 2017-04-14 2024-01-23 The United States Of America As Represented By The Department Of Veterans Affairs Compositions and methods for treating pulmonary fibrosis
BR112019026955A2 (en) 2017-06-22 2020-06-30 Pfizer Inc. dihydro-pyrrole-pyridine derivatives
CN107118157A (en) * 2017-06-23 2017-09-01 南京大学 The design and synthesis of diphenyl urea analog derivative antitumoral compounds of one class containing pyrazol framework
TW201908293A (en) 2017-07-12 2019-03-01 美商必治妥美雅史谷比公司 5 members of ROCK inhibitor and bicyclic heterocyclic guanamine
US11306081B2 (en) 2017-07-12 2022-04-19 Bristol-Myers Squibb Company Phenylacetamides as inhibitors of rock
EP3652165B1 (en) 2017-07-12 2021-08-25 Bristol-Myers Squibb Company Five membered-aminoheterocyclic and 5,6-or 6,6-membered bicyclic aminoheterocyclic inhibitors of rock for the treatment of heart failure
WO2019014304A1 (en) 2017-07-12 2019-01-17 Bristol-Myers Squibb Company Spiroheptanyl hydantoins as rock inhibitors
EP3694506B1 (en) * 2017-10-09 2023-08-02 Merck Sharp & Dohme LLC Novel substituted phenyloxetane and phenyltetrahydrofuran compounds as indoleamine 2,3-dioxygenase (ido) inhibitors
EP3873214A4 (en) 2018-10-29 2022-07-13 Forma Therapeutics, Inc. Solid forms of (4-(2-fluoro-4-(1-methyl-1 h-benzo[d]imidazol-5-yl)benzoyl) piperazin-1-yl)(1-hydroxycyclopropyl)methanone
WO2023245470A1 (en) * 2022-06-22 2023-12-28 南方医科大学珠江医院 Use of mdp analog in preparing medicament for treating inflammatory bowel disease

Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3535323A (en) * 1964-03-18 1970-10-20 Dresden Arzneimittel Amides of isoindoline-2-carboxylic acid
WO1995007271A1 (en) 1993-09-09 1995-03-16 The Upjohn Company Substituted oxazine and thiazine oxazolidinone antimicrobials
WO1997010223A1 (en) 1995-09-15 1997-03-20 Pharmacia & Upjohn Company Aminoaryl oxazolidinone n-oxides
US20050084506A1 (en) * 2003-08-06 2005-04-21 Catherine Tachdjian Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof
WO2005099353A2 (en) 2004-04-19 2005-10-27 Symed Labs Limited A novel process for the preparation of linezolid and related compounds
WO2006008754A1 (en) 2004-07-20 2006-01-26 Symed Labs Limited Novel intermediates for linezolid and related compounds
WO2007026920A2 (en) * 2005-09-02 2007-03-08 Astellas Pharma Inc. Amide derivatives as rock inhibitors
WO2007121124A2 (en) * 2006-04-11 2007-10-25 Novartis Ag Hcv inhibitors comprising beta amino acids and their uses
WO2007137955A1 (en) * 2006-05-30 2007-12-06 F. Hoffmann-La Roche Ag Piperidinyl pyrimidine derivatives
WO2008086047A1 (en) * 2007-01-03 2008-07-17 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
US7511013B2 (en) 2004-09-29 2009-03-31 Amr Technology, Inc. Cyclosporin analogues and their pharmaceutical uses
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US7514068B2 (en) 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
US20090093422A1 (en) 2006-10-23 2009-04-09 Roger Tung Oxazolidinone derivatives and methods of use
US7521421B2 (en) 1997-10-08 2009-04-21 Isotechnika Inc. Deuterated cyclosporine analogs and methods of making the same
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
US20090105147A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
US20090105307A1 (en) 2007-02-15 2009-04-23 Guido Galley 2-aminooxazolines as taar1 ligands
US20090111840A1 (en) 2005-05-31 2009-04-30 Peter Herold Heterocyclic spiro-compounds as aldosterone synthase inhibitors
US7528131B2 (en) 2007-04-19 2009-05-05 Concert Pharmaceuticals Inc. Substituted morpholinyl compounds
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US7531685B2 (en) 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US7534814B2 (en) 1999-07-30 2009-05-19 Nabriva Therapeutics Ag Mutilin derivatives and their use as antibacterials
US20090131363A1 (en) 2007-10-26 2009-05-21 Harbeson Scott L Deuterated darunavir
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090137457A1 (en) 2007-10-02 2009-05-28 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
WO2010066709A1 (en) * 2008-12-09 2010-06-17 Topotarget A/S Novel pyridinyl acrylamide derivatives

Family Cites Families (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH433312A (en) * 1963-10-18 1967-04-15 Dresden Arzneimittel Process for the preparation of therapeutically valuable amides of isoindoline-2-carboxylic acid
CH443312A (en) * 1963-10-29 1967-09-15 Ajinomoto Kk Process for the preparation of 1-N-oxide of hypoxanthine and 1-N-oxide of inosine, substituted or not, and use of the products obtained by this process for the use of the products obtained by this process for the preparation of 2,6- dichloropurine and 9-BD-ribofuranosyl purine, substituted or not
BE648616A (en) * 1964-05-29 1964-09-16 Dresden Arzneimittel Amides of isoindolin-2-carboxylic acids and their preparation process.
US4419360A (en) 1979-10-31 1983-12-06 Rohm And Haas Company Arthropod repellants
YU183090A (en) 1990-09-27 1992-12-21 Lek NEW N-ACYLDIPEPTIDES, PROCEDURES FOR THEIR PREPARATION AND PHARMACEUTICAL PREPARATIONS CONTAINING THEM
US5726197A (en) * 1992-11-02 1998-03-10 Syntex (U.S.A.) Inc. Isoindolinyl derivatives
AU4534696A (en) 1995-02-09 1996-08-27 Novo Nordisk A/S Compounds with growth hormone releasing properties
FR2733750B1 (en) 1995-05-03 1997-06-13 Synthelabo DERIVATIVES OF GAMMA-OXO-ALPHA- (PHENYLMETHYL) -5,6- DIHYDRO-4H-THIENO (3,4-C) PYRROLE-5-BUTANOIQUE, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
DE19624659A1 (en) 1996-06-20 1998-01-08 Klinge Co Chem Pharm Fab New pyridylalkene and pyridylalkanoic acid amides
DE19624668A1 (en) 1996-06-20 1998-02-19 Klinge Co Chem Pharm Fab Use of pyridylalkane, pyridylalken or pyridylalkynamides
US6677333B1 (en) 1999-01-26 2004-01-13 Ono Pharmaceutical Co., Ltd. 2H-phthalazin-1-one derivatives and drug containing its derivatives as active ingredient
EP1343796A4 (en) * 2000-10-23 2005-01-12 Smithkline Beecham Corp Compounds and methods
WO2002081443A1 (en) 2001-04-09 2002-10-17 Chiron Corporation Novel guanidino compounds
AU2002357692A1 (en) 2001-11-09 2003-05-26 Bristol-Myers Squibb Company Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity
JP2003277340A (en) 2002-03-22 2003-10-02 Toray Ind Inc Adhesive molecule inhibitor and new amino acid derivative
EP1348434A1 (en) 2002-03-27 2003-10-01 Fujisawa Deutschland GmbH Use of pyridyl amides as inhibitors of angiogenesis
TW200420559A (en) 2002-11-19 2004-10-16 Takeda Chemical Industries Ltd Amine compounds and method for producing the same
AU2004207731B2 (en) 2003-01-31 2009-08-13 Sanwa Kagaku Kenkyusho Co., Ltd. Compound inhibiting dipeptidyl peptidase iv
US7524837B2 (en) 2003-05-12 2009-04-28 Janssen Pharmaceutica N.V. Benzotriazapinone salts and methods for using same
GB0310865D0 (en) 2003-05-12 2003-06-18 Black James Foundation Gastrin and cholecystokinin receptor ligands
EP1660454A1 (en) 2003-07-07 2006-05-31 Vernalis (R&D) Limited Azacyclic compounds as inhibitors of sensory neurone specific channels
US20050256161A1 (en) 2003-08-13 2005-11-17 Tempest Paul A Melanin concentrating hormone receptor antagonists
EA011857B8 (en) * 2003-10-14 2012-08-30 Интермьюн, Инк. Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of hcv replication
US20080207685A1 (en) 2003-11-20 2008-08-28 Eli Lilly And Company Heterocyclic Compounds As Modulators Of Peroxisome Proliferator Activated Receptors, Useful For The Treatment And/Or Prevention Of Disorders Modulated By A Ppar
GB0329214D0 (en) 2003-12-17 2004-01-21 Glaxo Group Ltd Novel compounds
AP2006003763A0 (en) 2004-03-30 2006-10-31 Intermune Inc Macrocyclic compounds as inhibitors of viral replication
US20060045953A1 (en) 2004-08-06 2006-03-02 Catherine Tachdjian Aromatic amides and ureas and their uses as sweet and/or umami flavor modifiers, tastants and taste enhancers
EP1828134B1 (en) 2004-12-16 2008-10-29 F.Hoffmann-La Roche Ag Piperazinyl pyridine derivatives as anti-obesity agents
BRPI0519759A2 (en) * 2004-12-30 2009-03-10 Astex Therapeutics Ltd pharmaceutical compositions
MX2007013049A (en) * 2005-04-19 2008-01-11 Bayer Pharmaceuticals Corp Aryl alkyl acid derivatives for and use thereof.
WO2007011290A1 (en) 2005-07-18 2007-01-25 Respiratorius Ab Bronchorelaxing agents based on indol- and isoquinoline derivatives
KR20080067697A (en) 2005-11-11 2008-07-21 에프. 호프만-라 로슈 아게 Carbocyclic fused cyclic amines as inhibitors of the coagulation factor xa
WO2007076055A2 (en) 2005-12-22 2007-07-05 Entremed, Inc. Compositions and methods comprising proteinase activated receptor antagonists
JP4012239B2 (en) * 2006-01-11 2007-11-21 生化学工業株式会社 Oxazolone derivatives
JP4047365B2 (en) 2006-01-11 2008-02-13 生化学工業株式会社 Cycloalkanecarboxamide derivative and method for producing the same
EP1976840A1 (en) 2006-01-13 2008-10-08 F.Hoffmann-La Roche Ag Cyclohexyl piperazinyl methanone derivatives and their use as histamine h3 receptor modulators
KR101062513B1 (en) * 2006-02-17 2011-09-06 에프. 호프만-라 로슈 아게 Benzoyl-piperidine Derivatives as 5HT2 / D3 Modulators
MX2008014690A (en) 2006-05-18 2008-11-27 Hoffmann La Roche Thiazolo-pyramidine / pyridine urea derivatives as adenosine a2b receptor antagonists.
US8148417B2 (en) 2006-05-18 2012-04-03 Arena Pharmaceuticals, Inc. Primary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
WO2008027740A2 (en) 2006-08-29 2008-03-06 Office Of Intellectual Property And Technology Catalytic asymmetric synthesis of primary amines via borane reduction of oxime ethers using spiroborate esters
WO2008026018A1 (en) 2006-09-01 2008-03-06 Topotarget Switzerland Sa New method for the treatment of inflammatory diseases
WO2008104077A1 (en) 2007-02-28 2008-09-04 Methylgene Inc. Small molecule inhibitors of protein arginine methyltransferases (prmts)
GB0705882D0 (en) 2007-03-27 2007-05-02 Glaxo Group Ltd Novel compounds
WO2008130319A2 (en) 2007-04-23 2008-10-30 Astrazeneca Ab Novel n-tetrahydronaphtalene or n-chromane carboxamide derivatives for the treatment of pain
WO2009017838A2 (en) 2007-08-01 2009-02-05 Exelixis, Inc. Combinations of jak-2 inhibitors and other agents
RU2478094C2 (en) 2007-10-17 2013-03-27 Санофи-Авентис Substituted n-phenyl-bipyrrolidine ureas and therapeutic use thereof
GB0721332D0 (en) * 2007-10-31 2007-12-12 Motac Neuroscience Ltd Medicaments
EP2067771A1 (en) 2007-12-03 2009-06-10 EPFL Ecole Polytechnique Fédérale de Lausanne Derivatives of Dihydroxypyrrolidine as Anti-Cancer Compounds
EP2227461A1 (en) 2007-12-05 2010-09-15 AstraZeneca AB (Publ) New compounds iii
WO2009086835A1 (en) 2008-01-11 2009-07-16 Topotarget A/S Novel cyanoguanidines
JP2011088826A (en) * 2008-01-31 2011-05-06 Astellas Pharma Inc Aromatic carboxylic acid compound
EP2098231A1 (en) 2008-03-05 2009-09-09 Topotarget Switzerland SA Use of NAD formation inhibitors for the treatment of ischemia-reperfusion injury
WO2009118712A2 (en) 2008-03-27 2009-10-01 Ecole Polytechnique Federale De Lausanne (Epfl) Novel dihydroxypyrrolidine derivatives as anti-cancer agents
JP5816082B2 (en) 2008-06-24 2015-11-17 トポターゲット・アクティーゼルスカブＴｏｐｏＴａｒｇｅｔ Ａ／Ｓ Squaric acid derivatives as inhibitors of nicotinamide
RU2011111728A (en) 2008-08-29 2012-10-10 Топотаргет А/С (Dk) NEW DERIVATIVES OF UREA AND THIRE UREA
US20110318266A1 (en) 2008-09-16 2011-12-29 Mccauley John A Phthalimide derivative metabotropic glutamate r4 ligands
EP2350048A2 (en) 2008-10-16 2011-08-03 Schering Corporation Azine derivatives and methods of use thereof
WO2010057101A2 (en) * 2008-11-17 2010-05-20 Schering Corporation Compounds useful as hiv blockers
TW201030007A (en) 2009-02-06 2010-08-16 Gruenenthal Gmbh Substituted spiro-amides as b1r modulators
CA2759264A1 (en) 2009-04-21 2010-10-28 Astellas Pharma Inc. Diacylethylenediamine compound
ES2604305T3 (en) 2009-07-14 2017-03-06 Nerviano Medical Sciences S.R.L. 3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide with selective inhibition of PARP-1
KR20130044382A (en) 2010-03-01 2013-05-02 마이렉시스 인코포레이티드 Compounds and therapeutic uses thereof
MX342481B (en) 2010-09-03 2016-09-30 Genentech Inc * 4- { [ ( pyridin- 3 - yl -methyl) aminocarbonyl] amino} benzene - sulfone derivatives as nampt inhibitors for therapy of diseases such as cancer.
JP5881704B2 (en) 2010-09-03 2016-03-09 フォーマ ティーエム， エルエルシー． Novel compounds and compositions for inhibition of NAMPT
AU2011295727B2 (en) 2010-09-03 2015-04-02 Forma Tm, Llc. Guanidine compounds and compositions for the inhibition of NAMPT
US9302989B2 (en) * 2010-11-15 2016-04-05 Abbvie Inc. NAMPT and rock inhibitors

Patent Citations (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3535323A (en) * 1964-03-18 1970-10-20 Dresden Arzneimittel Amides of isoindoline-2-carboxylic acid
WO1995007271A1 (en) 1993-09-09 1995-03-16 The Upjohn Company Substituted oxazine and thiazine oxazolidinone antimicrobials
WO1997010223A1 (en) 1995-09-15 1997-03-20 Pharmacia & Upjohn Company Aminoaryl oxazolidinone n-oxides
US7538189B2 (en) 1997-10-08 2009-05-26 Isotechnika Inc. Methods of making deuterated cyclosporin analogs
US7521421B2 (en) 1997-10-08 2009-04-21 Isotechnika Inc. Deuterated cyclosporine analogs and methods of making the same
US7534814B2 (en) 1999-07-30 2009-05-19 Nabriva Therapeutics Ag Mutilin derivatives and their use as antibacterials
US20050084506A1 (en) * 2003-08-06 2005-04-21 Catherine Tachdjian Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof
WO2005099353A2 (en) 2004-04-19 2005-10-27 Symed Labs Limited A novel process for the preparation of linezolid and related compounds
WO2006008754A1 (en) 2004-07-20 2006-01-26 Symed Labs Limited Novel intermediates for linezolid and related compounds
US7511013B2 (en) 2004-09-29 2009-03-31 Amr Technology, Inc. Cyclosporin analogues and their pharmaceutical uses
US20090111840A1 (en) 2005-05-31 2009-04-30 Peter Herold Heterocyclic spiro-compounds as aldosterone synthase inhibitors
WO2007026920A2 (en) * 2005-09-02 2007-03-08 Astellas Pharma Inc. Amide derivatives as rock inhibitors
US7514068B2 (en) 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
WO2007121124A2 (en) * 2006-04-11 2007-10-25 Novartis Ag Hcv inhibitors comprising beta amino acids and their uses
WO2007137955A1 (en) * 2006-05-30 2007-12-06 F. Hoffmann-La Roche Ag Piperidinyl pyrimidine derivatives
US20090093422A1 (en) 2006-10-23 2009-04-09 Roger Tung Oxazolidinone derivatives and methods of use
WO2008086047A1 (en) * 2007-01-03 2008-07-17 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
US20090105307A1 (en) 2007-02-15 2009-04-23 Guido Galley 2-aminooxazolines as taar1 ligands
US7528131B2 (en) 2007-04-19 2009-05-05 Concert Pharmaceuticals Inc. Substituted morpholinyl compounds
US7531685B2 (en) 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
US20090137457A1 (en) 2007-10-02 2009-05-28 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
US20090105147A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
US20090131363A1 (en) 2007-10-26 2009-05-21 Harbeson Scott L Deuterated darunavir
WO2010066709A1 (en) * 2008-12-09 2010-06-17 Topotarget A/S Novel pyridinyl acrylamide derivatives

Non-Patent Citations (23)

* Cited by examiner, † Cited by third party
Title
ADYA, R., DIABETES CARE, vol. 31, 2008, pages 758 - 760
BLAGOJEVIC N ET AL.: "Dosimetry & Treatment Planning for Neutron Capture Therapy", 1994, ADVANCED MEDICAL PUBLISHING, pages: 125 - 134
BLAKE ET AL., J. PHARM. SCI., vol. 64, no. 3, 1975, pages 367 - 391
BRICKNER, S J ET AL., J MED CHEM, vol. 39, no. 3, 1996, pages 673
BUSSO, N. ET AL., PLOS ONE, vol. 3, 2008, pages E2267
CZAJKA D M; FINKEL A J, ANN. N.Y. ACAD. SCI., vol. 84, 1960, pages 770
CZAKJA D M ET AL., AM. J. PHYSIOL., vol. 201, 1961, pages 357
DIABETES METAB., vol. 23, 1997, pages 251
FOSTER ET AL.: "Advances in Drug Research", vol. 14, 1985, ACADEMIC PRESS, pages: 2 - 36
GALLI, M. ET AL., CANCER RES., vol. 70, 2010, pages 8 - 11
GARTEN, A. ET AL., TRENDS IN ENDOCRINOLOGY AND METABOLISM, vol. 20, 2008, pages 130 - 138
HANSEN, CM ET AL., ANTICANCER RES., vol. 20, 2000, pages 42111 - 4220
KATO ET AL., J. LABELLED COMP. RADIOPHARMACEUT., vol. 36, no. 10, 1995, pages 927 - 932
KIM, S.R. ET AL., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 357, 2007, pages 150 - 156
KUSHNER ET AL., CAN. J. PHYSIOL. PHARMACOL., vol. 77, 1999, pages 79 - 88
LIZONDO, J ET AL., DRUGS FUT, vol. 21, no. 11, 1996, pages 1116
MALLESHAM, B ET AL., ORG LETT, vol. 5, no. 7, 2003, pages 963
OLESE, U.H. ET AL., MOL CANCER THER., vol. 9, 2010, pages 1609 - 1617
See also references of EP2640698A1
SHOEB A ET AL: "STUDIES IN POSSIBLE ORAL HYPOGLYCAEMIC AGENTS: PART V-SYNTHESIS OF CARBAMOYLINDOLES, CARBAMOYLISOINDOLINES, 3-INDOLYLETHYL UREA (OR THIOUREA) & 2-ISOINDOLINYLPROPYL UREA (OR THIOUREA) DERIVATIVES & THEIR BIOLOGICAL ACTIVITY", INDIAN JOURNAL OF CHEMISTRY : IJC, COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH, IN, vol. 5, 1 April 1967 (1967-04-01), pages 142 - 144, XP009010912, ISSN: 0019-5103 *
THOMSON J F, ANN. NEW YORK ACAD. SCI, vol. 84, 1960, pages 736
VAN BEIJNUM, J.R. ET AL., INT. J. CANCER, vol. 101, 2002, pages 118 - 127
ZIEGKEL, M., EUR. J. BIOCHEM., vol. 267, 2000, pages 1550 - 1564

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9499563B2 (en) 2009-05-15 2016-11-22 Katholieke Universiteit Leuven Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors
US9132129B2 (en) 2010-11-15 2015-09-15 Katholieke Universiteit Leuven Antiviral compounds
US9266832B2 (en) 2010-12-13 2016-02-23 Katholieke Universiteit Levun Compounds for the treatment of neurodegenerative diseases
JP2013544872A (en) * 2010-12-13 2013-12-19 カソリック ユニヴェルシテイト ルーヴェン，ケー．ユー． ルーヴェン アール アンド ディー Novel compounds for the treatment of neurodegenerative diseases
US11479564B2 (en) 2011-05-09 2022-10-25 Valo Health, Inc. Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (NAMPT)
US9555039B2 (en) 2011-05-09 2017-01-31 Forma Tm, Llc. Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (NAMPT)
EP2776393A4 (en) * 2011-11-11 2015-05-27 Abbvie Inc Nampt inhibitors
WO2013067710A1 (en) 2011-11-11 2013-05-16 Abbott Laboratories Nampt inhibitors
US20160031813A1 (en) * 2011-11-11 2016-02-04 Michael L. Curtin Nampt Inhibitors
JP2015503594A (en) * 2012-01-09 2015-02-02 エックス−アールエックス，インコーポレーテッド Tryptoline derivative having kinase inhibitory activity and use thereof
AU2013208087B2 (en) * 2012-01-09 2017-11-23 X-Chem, Inc. Tryptoline derivatives having kinase inhibitory activity and uses thereof
JP2018058863A (en) * 2012-01-09 2018-04-12 エックス−アールエックス，インコーポレーテッド Tryptoline derivative having kinase inhibitor and use thereof
JP2013234180A (en) * 2012-04-13 2013-11-21 Mitsubishi Tanabe Pharma Corp Pharmaceutical application of amide derivative
JP2015528435A (en) * 2012-08-10 2015-09-28 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ Pyrazole carboxamide compounds, compositions and methods of use
EP2903618B1 (en) 2012-10-05 2022-06-01 Kadmon Corporation, LLC Rho kinase inhibitors
JP2019073521A (en) * 2013-01-18 2019-05-16 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Phthalazinones and isoquinolinones as rock inhibitors
JP2019077689A (en) * 2013-01-18 2019-05-23 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Phthalazinones and isoquinolinones as rock inhibitors
WO2014141035A3 (en) * 2013-03-11 2015-04-09 Aurigene Discovery Technologies Limited Fused heterocyclyl derivatives as nampt inhibitors
US9673344B2 (en) * 2014-08-07 2017-06-06 Lumeta, Llc Apparatus and method for photovoltaic module with tapered edge seal
US20210171513A1 (en) * 2016-03-17 2021-06-10 Checkmate Therapeutics Inc. Novel compound for inhibiting nicotinamide phosphoribosyltransferase and composition containing same
US11795163B2 (en) * 2016-03-17 2023-10-24 Checkmate Therapeutics Inc. Compound for inhibiting nicotinamide phosphoribosyltransferase and composition containing same
US11905284B2 (en) 2016-07-01 2024-02-20 Pfizer Inc. 5,7-dihydro-pyrrolo-pyridine derivatives
US11638762B2 (en) 2016-10-18 2023-05-02 Seagen Inc. Targeted delivery of nicotinamide adenine dinucleotide salvage pathway inhibitors
WO2018086703A1 (en) 2016-11-11 2018-05-17 Bayer Pharma Aktiengesellschaft Dihydropyridazinones substituted with phenylureas
US11931414B2 (en) 2017-04-27 2024-03-19 Seagen Inc. Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates
WO2019149637A1 (en) 2018-01-31 2019-08-08 Bayer Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
RU2732297C2 (en) * 2018-11-14 2020-09-15 Общество с ограниченной ответственностью "Гурус БиоФарм" Derivatives of non-steroid anti-inflammatory agents
WO2021013693A1 (en) 2019-07-23 2021-01-28 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
WO2022053651A2 (en) 2020-09-10 2022-03-17 Precirix N.V. Antibody fragment against fap
WO2023203135A1 (en) 2022-04-22 2023-10-26 Precirix N.V. Improved radiolabelled antibody
WO2023213801A1 (en) 2022-05-02 2023-11-09 Precirix N.V. Pre-targeting

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